ES2920886T3 - Agonistas de 5HT para el tratamiento de trastornos epilépticos - Google Patents
Agonistas de 5HT para el tratamiento de trastornos epilépticos Download PDFInfo
- Publication number
- ES2920886T3 ES2920886T3 ES16756282T ES16756282T ES2920886T3 ES 2920886 T3 ES2920886 T3 ES 2920886T3 ES 16756282 T ES16756282 T ES 16756282T ES 16756282 T ES16756282 T ES 16756282T ES 2920886 T3 ES2920886 T3 ES 2920886T3
- Authority
- ES
- Spain
- Prior art keywords
- receptor agonist
- pharmaceutically acceptable
- subject
- administered
- seizures
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000952 serotonin receptor agonist Substances 0.000 title claims abstract description 234
- 230000001037 epileptic effect Effects 0.000 title claims abstract description 75
- 238000011282 treatment Methods 0.000 title claims description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 190
- 238000000034 method Methods 0.000 claims abstract description 60
- 206010010904 Convulsion Diseases 0.000 claims description 162
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 140
- 230000000694 effects Effects 0.000 claims description 107
- 239000001961 anticonvulsive agent Substances 0.000 claims description 105
- 229960003965 antiepileptics Drugs 0.000 claims description 73
- 206010015037 epilepsy Diseases 0.000 claims description 60
- 208000036572 Myoclonic epilepsy Diseases 0.000 claims description 50
- 201000007547 Dravet syndrome Diseases 0.000 claims description 45
- 206010073677 Severe myoclonic epilepsy of infancy Diseases 0.000 claims description 45
- -1 cannabadiols Chemical compound 0.000 claims description 43
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 28
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 claims description 24
- 229960001897 stiripentol Drugs 0.000 claims description 19
- IBLNKMRFIPWSOY-FNORWQNLSA-N stiripentol Chemical compound CC(C)(C)C(O)\C=C\C1=CC=C2OCOC2=C1 IBLNKMRFIPWSOY-FNORWQNLSA-N 0.000 claims description 19
- 229940049706 benzodiazepine Drugs 0.000 claims description 17
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 claims description 17
- PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 claims description 16
- 229960000623 carbamazepine Drugs 0.000 claims description 15
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 claims description 15
- 229960003991 trazodone Drugs 0.000 claims description 15
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 claims description 13
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 claims description 13
- XTTZERNUQAFMOF-QMMMGPOBSA-N lorcaserin Chemical compound C[C@H]1CNCCC2=CC=C(Cl)C=C12 XTTZERNUQAFMOF-QMMMGPOBSA-N 0.000 claims description 13
- 229960004394 topiramate Drugs 0.000 claims description 13
- 229960002870 gabapentin Drugs 0.000 claims description 12
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 claims description 12
- 229960005060 lorcaserin Drugs 0.000 claims description 12
- 229960001816 oxcarbazepine Drugs 0.000 claims description 12
- CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 claims description 12
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 claims description 11
- 230000037396 body weight Effects 0.000 claims description 11
- 229960002767 ethosuximide Drugs 0.000 claims description 11
- HAPOVYFOVVWLRS-UHFFFAOYSA-N ethosuximide Chemical compound CCC1(C)CC(=O)NC1=O HAPOVYFOVVWLRS-UHFFFAOYSA-N 0.000 claims description 11
- 229960001582 fenfluramine Drugs 0.000 claims description 11
- 235000020887 ketogenic diet Nutrition 0.000 claims description 11
- 229960001848 lamotrigine Drugs 0.000 claims description 11
- 229940094035 potassium bromide Drugs 0.000 claims description 11
- 229940084026 sodium valproate Drugs 0.000 claims description 11
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 10
- 201000006792 Lennox-Gastaut syndrome Diseases 0.000 claims description 10
- 229960004002 levetiracetam Drugs 0.000 claims description 10
- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 claims description 10
- PGTVWKLGGCQMBR-FLBATMFCSA-N Ganaxolone Chemical compound C([C@@H]1CC2)[C@](C)(O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 PGTVWKLGGCQMBR-FLBATMFCSA-N 0.000 claims description 9
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 claims description 9
- 229960003120 clonazepam Drugs 0.000 claims description 9
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 claims description 9
- 229960003472 felbamate Drugs 0.000 claims description 9
- WKGXYQFOCVYPAC-UHFFFAOYSA-N felbamate Chemical compound NC(=O)OCC(COC(N)=O)C1=CC=CC=C1 WKGXYQFOCVYPAC-UHFFFAOYSA-N 0.000 claims description 9
- 229950006567 ganaxolone Drugs 0.000 claims description 9
- 229960002695 phenobarbital Drugs 0.000 claims description 9
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 claims description 9
- 229960002036 phenytoin Drugs 0.000 claims description 9
- 229960001233 pregabalin Drugs 0.000 claims description 9
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 claims description 9
- 229960002393 primidone Drugs 0.000 claims description 9
- DQMZLTXERSFNPB-UHFFFAOYSA-N primidone Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NCNC1=O DQMZLTXERSFNPB-UHFFFAOYSA-N 0.000 claims description 9
- 229960001918 tiagabine Drugs 0.000 claims description 9
- PBJUNZJWGZTSKL-MRXNPFEDSA-N tiagabine Chemical compound C1=CSC(C(=CCCN2C[C@@H](CCC2)C(O)=O)C2=C(C=CS2)C)=C1C PBJUNZJWGZTSKL-MRXNPFEDSA-N 0.000 claims description 9
- 229960002911 zonisamide Drugs 0.000 claims description 9
- UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 claims description 9
- 231100000867 compulsive behavior Toxicity 0.000 claims description 8
- PJDFLNIOAUIZSL-UHFFFAOYSA-N vigabatrin Chemical compound C=CC(N)CCC(O)=O PJDFLNIOAUIZSL-UHFFFAOYSA-N 0.000 claims description 8
- 229960005318 vigabatrin Drugs 0.000 claims description 8
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
- 229960000571 acetazolamide Drugs 0.000 claims description 7
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 claims description 7
- 229960001403 clobazam Drugs 0.000 claims description 7
- CXOXHMZGEKVPMT-UHFFFAOYSA-N clobazam Chemical compound O=C1CC(=O)N(C)C2=CC=C(Cl)C=C2N1C1=CC=CC=C1 CXOXHMZGEKVPMT-UHFFFAOYSA-N 0.000 claims description 7
- GMZVRMREEHBGGF-UHFFFAOYSA-N Piracetam Chemical compound NC(=O)CN1CCCC1=O GMZVRMREEHBGGF-UHFFFAOYSA-N 0.000 claims description 6
- 238000011360 adjunctive therapy Methods 0.000 claims description 6
- PCOBBVZJEWWZFR-UHFFFAOYSA-N ezogabine Chemical compound C1=C(N)C(NC(=O)OCC)=CC=C1NCC1=CC=C(F)C=C1 PCOBBVZJEWWZFR-UHFFFAOYSA-N 0.000 claims description 6
- 229960002623 lacosamide Drugs 0.000 claims description 6
- VPPJLAIAVCUEMN-GFCCVEGCSA-N lacosamide Chemical compound COC[C@@H](NC(C)=O)C(=O)NCC1=CC=CC=C1 VPPJLAIAVCUEMN-GFCCVEGCSA-N 0.000 claims description 6
- 229960001454 nitrazepam Drugs 0.000 claims description 6
- KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 claims description 6
- 229960004526 piracetam Drugs 0.000 claims description 6
- 229960003312 retigabine Drugs 0.000 claims description 6
- POGQSBRIGCQNEG-UHFFFAOYSA-N rufinamide Chemical compound N1=NC(C(=O)N)=CN1CC1=C(F)C=CC=C1F POGQSBRIGCQNEG-UHFFFAOYSA-N 0.000 claims description 6
- 229960003014 rufinamide Drugs 0.000 claims description 6
- 208000005809 status epilepticus Diseases 0.000 claims description 6
- ZRJBHWIHUMBLCN-SEQYCRGISA-N Huperzine A Natural products N1C(=O)C=CC2=C1C[C@H]1/C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-SEQYCRGISA-N 0.000 claims description 5
- ZRJBHWIHUMBLCN-UHFFFAOYSA-N Shuangyiping Natural products N1C(=O)C=CC2=C1CC1C(=CC)C2(N)CC(C)=C1 ZRJBHWIHUMBLCN-UHFFFAOYSA-N 0.000 claims description 5
- QIALRBLEEWJACW-INIZCTEOSA-N eslicarbazepine acetate Chemical compound CC(=O)O[C@H]1CC2=CC=CC=C2N(C(N)=O)C2=CC=CC=C12 QIALRBLEEWJACW-INIZCTEOSA-N 0.000 claims description 5
- 229960003233 eslicarbazepine acetate Drugs 0.000 claims description 5
- SZQIFWWUIBRPBZ-UHFFFAOYSA-N ethotoin Chemical compound O=C1N(CC)C(=O)NC1C1=CC=CC=C1 SZQIFWWUIBRPBZ-UHFFFAOYSA-N 0.000 claims description 5
- 229960003533 ethotoin Drugs 0.000 claims description 5
- ZRJBHWIHUMBLCN-YQEJDHNASA-N huperzine A Chemical compound N1C(=O)C=CC2=C1C[C@H]1\C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-YQEJDHNASA-N 0.000 claims description 5
- 229960005198 perampanel Drugs 0.000 claims description 5
- PRMWGUBFXWROHD-UHFFFAOYSA-N perampanel Chemical compound O=C1C(C=2C(=CC=CC=2)C#N)=CC(C=2N=CC=CC=2)=CN1C1=CC=CC=C1 PRMWGUBFXWROHD-UHFFFAOYSA-N 0.000 claims description 5
- ZRJBHWIHUMBLCN-BMIGLBTASA-N rac-huperzine A Natural products N1C(=O)C=CC2=C1C[C@@H]1C(=CC)[C@@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-BMIGLBTASA-N 0.000 claims description 5
- OHHDIOKRWWOXMT-UHFFFAOYSA-N trazodone hydrochloride Chemical group [H+].[Cl-].ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 OHHDIOKRWWOXMT-UHFFFAOYSA-N 0.000 claims description 2
- 229960002301 trazodone hydrochloride Drugs 0.000 claims description 2
- 235000002639 sodium chloride Nutrition 0.000 description 191
- 150000001875 compounds Chemical class 0.000 description 108
- 241000252212 Danio rerio Species 0.000 description 100
- 208000035475 disorder Diseases 0.000 description 91
- 239000003814 drug Substances 0.000 description 57
- 108090000623 proteins and genes Proteins 0.000 description 55
- CJXAEXPPLWQRFR-UHFFFAOYSA-N clemizole Chemical compound C1=CC(Cl)=CC=C1CN1C2=CC=CC=C2N=C1CN1CCCC1 CJXAEXPPLWQRFR-UHFFFAOYSA-N 0.000 description 53
- 229940079593 drug Drugs 0.000 description 53
- 239000000203 mixture Substances 0.000 description 51
- 230000014509 gene expression Effects 0.000 description 49
- 239000008194 pharmaceutical composition Substances 0.000 description 49
- 201000010099 disease Diseases 0.000 description 44
- 230000033001 locomotion Effects 0.000 description 41
- 108091006146 Channels Proteins 0.000 description 39
- 230000006399 behavior Effects 0.000 description 37
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 36
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 36
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 34
- 229950002020 clemizole Drugs 0.000 description 31
- 238000003556 assay Methods 0.000 description 30
- 238000009472 formulation Methods 0.000 description 29
- 102000005962 receptors Human genes 0.000 description 29
- 108020003175 receptors Proteins 0.000 description 29
- 238000012360 testing method Methods 0.000 description 29
- 230000006870 function Effects 0.000 description 28
- 239000000243 solution Substances 0.000 description 28
- 101000631760 Homo sapiens Sodium channel protein type 1 subunit alpha Proteins 0.000 description 27
- 241000251468 Actinopterygii Species 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 24
- 230000002269 spontaneous effect Effects 0.000 description 23
- 230000004044 response Effects 0.000 description 21
- 210000004556 brain Anatomy 0.000 description 20
- 230000008859 change Effects 0.000 description 20
- 230000035772 mutation Effects 0.000 description 20
- 241001465754 Metazoa Species 0.000 description 19
- 102100028910 Sodium channel protein type 1 subunit alpha Human genes 0.000 description 19
- 230000009182 swimming Effects 0.000 description 19
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 17
- 239000011575 calcium Substances 0.000 description 17
- 210000003169 central nervous system Anatomy 0.000 description 16
- 239000003112 inhibitor Substances 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- 230000001418 larval effect Effects 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 15
- 229940076279 serotonin Drugs 0.000 description 15
- 102100027282 Fanconi anemia group E protein Human genes 0.000 description 14
- 239000000556 agonist Substances 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 230000007812 deficiency Effects 0.000 description 14
- 208000013257 developmental and epileptic encephalopathy Diseases 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- 208000024891 symptom Diseases 0.000 description 14
- 238000001727 in vivo Methods 0.000 description 13
- 238000001990 intravenous administration Methods 0.000 description 13
- 239000003826 tablet Substances 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- 239000002775 capsule Substances 0.000 description 12
- 239000000839 emulsion Substances 0.000 description 12
- 230000001965 increasing effect Effects 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 239000002287 radioligand Substances 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 238000012216 screening Methods 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000013543 active substance Substances 0.000 description 11
- 230000001773 anti-convulsant effect Effects 0.000 description 11
- 239000000739 antihistaminic agent Substances 0.000 description 11
- 230000003137 locomotive effect Effects 0.000 description 11
- 206010021750 Infantile Spasms Diseases 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 238000000692 Student's t-test Methods 0.000 description 10
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 10
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 10
- 210000004129 prosencephalon Anatomy 0.000 description 10
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 10
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 10
- 238000010200 validation analysis Methods 0.000 description 10
- 208000024827 Alzheimer disease Diseases 0.000 description 9
- 206010003805 Autism Diseases 0.000 description 9
- 208000020706 Autistic disease Diseases 0.000 description 9
- 102000012276 GABA Plasma Membrane Transport Proteins Human genes 0.000 description 9
- 108091006228 GABA transporters Proteins 0.000 description 9
- 241000282412 Homo Species 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 210000002216 heart Anatomy 0.000 description 9
- 239000002502 liposome Substances 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 208000002091 Febrile Seizures Diseases 0.000 description 8
- 208000018737 Parkinson disease Diseases 0.000 description 8
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 description 8
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 description 8
- 208000003554 absence epilepsy Diseases 0.000 description 8
- 229940125715 antihistaminic agent Drugs 0.000 description 8
- 239000003086 colorant Substances 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 201000009028 early myoclonic encephalopathy Diseases 0.000 description 8
- 238000010172 mouse model Methods 0.000 description 8
- 229960005152 pentetrazol Drugs 0.000 description 8
- 239000000018 receptor agonist Substances 0.000 description 8
- 229940044601 receptor agonist Drugs 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 230000001988 toxicity Effects 0.000 description 8
- 231100000419 toxicity Toxicity 0.000 description 8
- 206010020843 Hyperthermia Diseases 0.000 description 7
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 7
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 7
- YGCODSQDUUUKIV-UHFFFAOYSA-N Zoxazolamine Chemical compound ClC1=CC=C2OC(N)=NC2=C1 YGCODSQDUUUKIV-UHFFFAOYSA-N 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 230000001154 acute effect Effects 0.000 description 7
- 230000003556 anti-epileptic effect Effects 0.000 description 7
- 210000004204 blood vessel Anatomy 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 229960003529 diazepam Drugs 0.000 description 7
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 7
- 235000014113 dietary fatty acids Nutrition 0.000 description 7
- 239000003937 drug carrier Substances 0.000 description 7
- 230000001787 epileptiform Effects 0.000 description 7
- 239000000194 fatty acid Substances 0.000 description 7
- 229930195729 fatty acid Natural products 0.000 description 7
- 230000002068 genetic effect Effects 0.000 description 7
- 230000036031 hyperthermia Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 231100000350 mutagenesis Toxicity 0.000 description 7
- 238000002703 mutagenesis Methods 0.000 description 7
- 230000001537 neural effect Effects 0.000 description 7
- 230000000144 pharmacologic effect Effects 0.000 description 7
- 239000006187 pill Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000000829 suppository Substances 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 229920001817 Agar Polymers 0.000 description 6
- 208000019901 Anxiety disease Diseases 0.000 description 6
- 201000008009 Early infantile epileptic encephalopathy Diseases 0.000 description 6
- 206010071545 Early infantile epileptic encephalopathy with burst-suppression Diseases 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 206010071082 Juvenile myoclonic epilepsy Diseases 0.000 description 6
- 208000037158 Partial Epilepsies Diseases 0.000 description 6
- 102000018674 Sodium Channels Human genes 0.000 description 6
- 108010052164 Sodium Channels Proteins 0.000 description 6
- 206010047139 Vasoconstriction Diseases 0.000 description 6
- 201000006791 West syndrome Diseases 0.000 description 6
- 230000002411 adverse Effects 0.000 description 6
- 239000008272 agar Substances 0.000 description 6
- 235000010419 agar Nutrition 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 229940125681 anticonvulsant agent Drugs 0.000 description 6
- 230000036506 anxiety Effects 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 208000034287 idiopathic generalized susceptibility to 7 epilepsy Diseases 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 210000001153 interneuron Anatomy 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 239000007937 lozenge Substances 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 230000036961 partial effect Effects 0.000 description 6
- 230000019491 signal transduction Effects 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 229940102566 valproate Drugs 0.000 description 6
- 230000025033 vasoconstriction Effects 0.000 description 6
- 229950006967 zoxazolamine Drugs 0.000 description 6
- PYJBJMIBANAOFJ-UHFFFAOYSA-N 1-[5-(thiophen-2-ylmethoxy)-1h-indol-3-yl]propan-2-amine;hydrochloride Chemical compound Cl.C1=C2C(CC(N)C)=CNC2=CC=C1OCC1=CC=CS1 PYJBJMIBANAOFJ-UHFFFAOYSA-N 0.000 description 5
- FSKFPVLPFLJRQB-UHFFFAOYSA-N 2-methyl-1-(4-methylphenyl)-3-(1-piperidinyl)-1-propanone Chemical compound C=1C=C(C)C=CC=1C(=O)C(C)CN1CCCCC1 FSKFPVLPFLJRQB-UHFFFAOYSA-N 0.000 description 5
- 102000006969 5-HT2B Serotonin Receptor Human genes 0.000 description 5
- 108010072584 5-HT2B Serotonin Receptor Proteins 0.000 description 5
- 241000416162 Astragalus gummifer Species 0.000 description 5
- 208000001914 Fragile X syndrome Diseases 0.000 description 5
- 238000011529 RT qPCR Methods 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 229920001615 Tragacanth Polymers 0.000 description 5
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 5
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 description 5
- 238000011260 co-administration Methods 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 238000007876 drug discovery Methods 0.000 description 5
- 238000007877 drug screening Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 229960002053 flibanserin Drugs 0.000 description 5
- 238000007918 intramuscular administration Methods 0.000 description 5
- 210000001161 mammalian embryo Anatomy 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 229920000609 methyl cellulose Polymers 0.000 description 5
- 239000001923 methylcellulose Substances 0.000 description 5
- 235000010981 methylcellulose Nutrition 0.000 description 5
- 238000002493 microarray Methods 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 230000007958 sleep Effects 0.000 description 5
- 150000003384 small molecules Chemical class 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 229960005334 tolperisone Drugs 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- MLBHFBKZUPLWBD-UHFFFAOYSA-N 1-[3-(trifluoromethyl)phenyl]-2-propanamine Chemical compound CC(N)CC1=CC=CC(C(F)(F)F)=C1 MLBHFBKZUPLWBD-UHFFFAOYSA-N 0.000 description 4
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 4
- 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 4
- 108010071131 Autoreceptors Proteins 0.000 description 4
- 102000007527 Autoreceptors Human genes 0.000 description 4
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 4
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 4
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 description 4
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 description 4
- 208000003449 Classical Lissencephalies and Subcortical Band Heterotopias Diseases 0.000 description 4
- 206010012335 Dependence Diseases 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- XWLUWCNOOVRFPX-UHFFFAOYSA-N Fosphenytoin Chemical compound O=C1N(COP(O)(=O)O)C(=O)NC1(C=1C=CC=CC=1)C1=CC=CC=C1 XWLUWCNOOVRFPX-UHFFFAOYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 201000008189 Juvenile absence epilepsy Diseases 0.000 description 4
- 206010061334 Partial seizures Diseases 0.000 description 4
- 108010012996 Serotonin Plasma Membrane Transport Proteins Proteins 0.000 description 4
- 102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 230000001387 anti-histamine Effects 0.000 description 4
- 230000036528 appetite Effects 0.000 description 4
- 235000019789 appetite Nutrition 0.000 description 4
- 230000003542 behavioural effect Effects 0.000 description 4
- 201000003452 benign familial neonatal epilepsy Diseases 0.000 description 4
- 201000010295 benign neonatal seizures Diseases 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 208000029078 coronary artery disease Diseases 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 206010014599 encephalitis Diseases 0.000 description 4
- 230000012202 endocytosis Effects 0.000 description 4
- 229940011871 estrogen Drugs 0.000 description 4
- 239000000262 estrogen Substances 0.000 description 4
- 235000019634 flavors Nutrition 0.000 description 4
- PPRRDFIXUUSXRA-UHFFFAOYSA-N flibanserin Chemical compound FC(F)(F)C1=CC=CC(N2CCN(CCN3C(NC4=CC=CC=C43)=O)CC2)=C1 PPRRDFIXUUSXRA-UHFFFAOYSA-N 0.000 description 4
- 235000003599 food sweetener Nutrition 0.000 description 4
- 229960000693 fosphenytoin Drugs 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 208000019622 heart disease Diseases 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 4
- 208000013403 hyperactivity Diseases 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 238000007913 intrathecal administration Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 238000010208 microarray analysis Methods 0.000 description 4
- 239000004005 microsphere Substances 0.000 description 4
- 230000036651 mood Effects 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 239000006072 paste Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 201000005070 reflex epilepsy Diseases 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- 230000009329 sexual behaviour Effects 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 239000003765 sweetening agent Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 3
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 3
- 244000215068 Acacia senegal Species 0.000 description 3
- 208000009575 Angelman syndrome Diseases 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 101100401560 Drosophila melanogaster mib1 gene Proteins 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 102000018899 Glutamate Receptors Human genes 0.000 description 3
- 108010027915 Glutamate Receptors Proteins 0.000 description 3
- 108091006065 Gs proteins Proteins 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 208000019695 Migraine disease Diseases 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- 208000025966 Neurological disease Diseases 0.000 description 3
- 102400000064 Neuropeptide Y Human genes 0.000 description 3
- 208000008589 Obesity Diseases 0.000 description 3
- 206010033799 Paralysis Diseases 0.000 description 3
- 208000012641 Pigmentation disease Diseases 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- 208000033063 Progressive myoclonic epilepsy Diseases 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 102000003567 TRPV4 Human genes 0.000 description 3
- 101150098315 TRPV4 gene Proteins 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 238000000540 analysis of variance Methods 0.000 description 3
- 210000003050 axon Anatomy 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 210000001638 cerebellum Anatomy 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- BTFHLQRNAMSNLC-UHFFFAOYSA-N clorgyline Chemical compound C#CCN(C)CCCOC1=CC=C(Cl)C=C1Cl BTFHLQRNAMSNLC-UHFFFAOYSA-N 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 230000007831 electrophysiology Effects 0.000 description 3
- 238000002001 electrophysiology Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 208000028316 focal seizure Diseases 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 238000013537 high throughput screening Methods 0.000 description 3
- 230000000971 hippocampal effect Effects 0.000 description 3
- 238000007901 in situ hybridization Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 235000015110 jellies Nutrition 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 150000002611 lead compounds Chemical class 0.000 description 3
- 231100000518 lethal Toxicity 0.000 description 3
- 230000001665 lethal effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000015654 memory Effects 0.000 description 3
- 239000003158 myorelaxant agent Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 235000020824 obesity Nutrition 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000003973 paint Substances 0.000 description 3
- 230000018052 penile erection Effects 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000012353 t test Methods 0.000 description 3
- 210000001587 telencephalon Anatomy 0.000 description 3
- 230000028016 temperature homeostasis Effects 0.000 description 3
- 239000002562 thickening agent Substances 0.000 description 3
- 235000010487 tragacanth Nutrition 0.000 description 3
- 239000000196 tragacanth Substances 0.000 description 3
- 229940116362 tragacanth Drugs 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- INGCLXPSKXSYND-BTJKTKAUSA-N (z)-but-2-enedioic acid;3-(1-methylpiperidin-4-yl)-1h-indol-5-ol Chemical compound OC(=O)\C=C/C(O)=O.C1CN(C)CCC1C1=CNC2=CC=C(O)C=C12 INGCLXPSKXSYND-BTJKTKAUSA-N 0.000 description 2
- QVFDMWGKHUFODK-UHFFFAOYSA-N 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine;hydrochloride Chemical compound Cl.COC1=CC(CC(C)N)=C(OC)C=C1I QVFDMWGKHUFODK-UHFFFAOYSA-N 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- XBGUIVFBMBVUEG-UHFFFAOYSA-N 1-methyl-4-(1,5-dimethyl-4-hexenylidene)-1-cyclohexene Chemical compound CC(C)=CCCC(C)=C1CCC(C)=CC1 XBGUIVFBMBVUEG-UHFFFAOYSA-N 0.000 description 2
- WKNFADCGOAHBPG-UHFFFAOYSA-N 3-(1-methyl-4-piperidinyl)-1H-indol-5-ol Chemical compound C1CN(C)CCC1C1=CNC2=CC=C(O)C=C12 WKNFADCGOAHBPG-UHFFFAOYSA-N 0.000 description 2
- QJHCTHPYUOXOGM-UHFFFAOYSA-N 3-[4-(3-chlorophenyl)piperazin-1-yl]-1,1-diphenylpropan-2-ol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)C(O)CN(CC1)CCN1C1=CC=CC(Cl)=C1 QJHCTHPYUOXOGM-UHFFFAOYSA-N 0.000 description 2
- MWJWBEUGJSWXGZ-UHFFFAOYSA-N 3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenylpropan-2-ol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)C(O)CN(CC1)CCN1C1=CC=C(Cl)C=C1 MWJWBEUGJSWXGZ-UHFFFAOYSA-N 0.000 description 2
- PDWNVVUANMHHOR-UHFFFAOYSA-N 3-bromo-2,5-dimethoxy-N-methylbicyclo[4.2.0]octa-1(6),2,4,7-tetraen-7-amine hydrobromide Chemical compound Br.COC1=CC(Br)=C(OC)C2=C1C(NC)=C2 PDWNVVUANMHHOR-UHFFFAOYSA-N 0.000 description 2
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 2
- 102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 description 2
- 101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 description 2
- AYYCFGDXLUPJAQ-UHFFFAOYSA-N 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione Chemical compound COC1=CC=CC=C1N1CCN(CCN2C(CC3(CCCC3)CC2=O)=O)CC1 AYYCFGDXLUPJAQ-UHFFFAOYSA-N 0.000 description 2
- 206010052075 Acquired epileptic aphasia Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 206010054895 Baltic myoclonic epilepsy Diseases 0.000 description 2
- 206010070530 Benign rolandic epilepsy Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 102100033868 Cannabinoid receptor 1 Human genes 0.000 description 2
- 101710187010 Cannabinoid receptor 1 Proteins 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 2
- 208000006029 Cardiomegaly Diseases 0.000 description 2
- 229920001287 Chondroitin sulfate Polymers 0.000 description 2
- 206010070666 Cortical dysplasia Diseases 0.000 description 2
- 244000163122 Curcuma domestica Species 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 208000001654 Drug Resistant Epilepsy Diseases 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 229940124602 FDA-approved drug Drugs 0.000 description 2
- 206010016173 Fall Diseases 0.000 description 2
- 201000009010 Frontal lobe epilepsy Diseases 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 102000005915 GABA Receptors Human genes 0.000 description 2
- 108010005551 GABA Receptors Proteins 0.000 description 2
- 208000003078 Generalized Epilepsy Diseases 0.000 description 2
- 108091006101 Gi proteins Proteins 0.000 description 2
- 108091006067 Goα proteins Proteins 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 108010077223 Homer Scaffolding Proteins Proteins 0.000 description 2
- 102000010029 Homer Scaffolding Proteins Human genes 0.000 description 2
- 101000654381 Homo sapiens Sodium channel protein type 8 subunit alpha Proteins 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 208000035899 Infantile spasms syndrome Diseases 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- 201000006347 Intellectual Disability Diseases 0.000 description 2
- 201000005802 Landau-Kleffner Syndrome Diseases 0.000 description 2
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 2
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 201000004246 Miller-Dieker lissencephaly syndrome Diseases 0.000 description 2
- 208000035022 Miller-Dieker syndrome Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 208000002033 Myoclonus Diseases 0.000 description 2
- FUSGACRLAFQQRL-UHFFFAOYSA-N N-Ethyl-N-nitrosourea Chemical compound CCN(N=O)C(N)=O FUSGACRLAFQQRL-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 101800001019 Non-structural protein 4B Proteins 0.000 description 2
- 238000010222 PCR analysis Methods 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 108060005874 Parvalbumin Proteins 0.000 description 2
- 102000001675 Parvalbumin Human genes 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 201000010769 Prader-Willi syndrome Diseases 0.000 description 2
- 208000033255 Progressive myoclonic epilepsy type 1 Diseases 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- 206010071141 Rasmussen encephalitis Diseases 0.000 description 2
- 208000004160 Rasmussen subacute encephalitis Diseases 0.000 description 2
- 208000004974 Rolandic Epilepsy Diseases 0.000 description 2
- 101150022529 Scn1a gene Proteins 0.000 description 2
- 102100031371 Sodium channel protein type 8 subunit alpha Human genes 0.000 description 2
- 108050007677 Somatolactin Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 208000006657 Unverricht-Lundborg syndrome Diseases 0.000 description 2
- ICMGLRUYEQNHPF-UHFFFAOYSA-N Uraprene Chemical compound COC1=CC=CC=C1N1CCN(CCCNC=2N(C(=O)N(C)C(=O)C=2)C)CC1 ICMGLRUYEQNHPF-UHFFFAOYSA-N 0.000 description 2
- 201000006793 Walker-Warburg syndrome Diseases 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000011374 additional therapy Methods 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000016571 aggressive behavior Effects 0.000 description 2
- YHBUQBJHSRGZNF-HNNXBMFYSA-N alpha-bisabolene Natural products CC(C)=CCC=C(C)[C@@H]1CCC(C)=CC1 YHBUQBJHSRGZNF-HNNXBMFYSA-N 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- VHGCDTVCOLNTBX-QGZVFWFLSA-N atomoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=CC=C1C VHGCDTVCOLNTBX-QGZVFWFLSA-N 0.000 description 2
- 229960002430 atomoxetine Drugs 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 201000008916 benign epilepsy with centrotemporal spikes Diseases 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000008512 biological response Effects 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 229930003493 bisabolene Natural products 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 2
- 229960002495 buspirone Drugs 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 230000009084 cardiovascular function Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 208000033205 childhood epilepsy with centrotemporal spikes Diseases 0.000 description 2
- 229940059329 chondroitin sulfate Drugs 0.000 description 2
- DCSUBABJRXZOMT-IRLDBZIGSA-N cisapride Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)OC)N1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-IRLDBZIGSA-N 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 230000002920 convulsive effect Effects 0.000 description 2
- 235000003373 curcuma longa Nutrition 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 230000008579 epileptogenesis Effects 0.000 description 2
- OFKDAAIKGIBASY-VFGNJEKYSA-N ergotamine Chemical compound C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C3=CC=CC4=NC=C([C]34)C2)=C1)C)C1=CC=CC=C1 OFKDAAIKGIBASY-VFGNJEKYSA-N 0.000 description 2
- 229960004943 ergotamine Drugs 0.000 description 2
- XCGSFFUVFURLIX-UHFFFAOYSA-N ergotaminine Natural products C1=C(C=2C=CC=C3NC=C(C=23)C2)C2N(C)CC1C(=O)NC(C(N12)=O)(C)OC1(O)C1CCCN1C(=O)C2CC1=CC=CC=C1 XCGSFFUVFURLIX-UHFFFAOYSA-N 0.000 description 2
- 230000002964 excitative effect Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 201000007186 focal epilepsy Diseases 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 230000003371 gabaergic effect Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 2
- 239000000938 histamine H1 antagonist Substances 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- NIBOMXUDFLRHRV-UHFFFAOYSA-N hydron;8-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-8-azaspiro[4.5]decane-7,9-dione;dichloride Chemical compound Cl.Cl.COC1=CC=CC=C1N1CCN(CCN2C(CC3(CCCC3)CC2=O)=O)CC1 NIBOMXUDFLRHRV-UHFFFAOYSA-N 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 201000001993 idiopathic generalized epilepsy Diseases 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 210000001926 inhibitory interneuron Anatomy 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000002109 interictal effect Effects 0.000 description 2
- 230000007653 larval development Effects 0.000 description 2
- 230000013016 learning Effects 0.000 description 2
- 231100000225 lethality Toxicity 0.000 description 2
- 230000002197 limbic effect Effects 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 2
- 239000001095 magnesium carbonate Substances 0.000 description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 2
- 235000014380 magnesium carbonate Nutrition 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 230000001617 migratory effect Effects 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 229960001785 mirtazapine Drugs 0.000 description 2
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 108010043412 neuropeptide Y-Y1 receptor Proteins 0.000 description 2
- 231100000956 nontoxicity Toxicity 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 238000001422 normality test Methods 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000001314 paroxysmal effect Effects 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- 239000001814 pectin Substances 0.000 description 2
- 229920001277 pectin Polymers 0.000 description 2
- 235000010987 pectin Nutrition 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 201000003040 photosensitive epilepsy Diseases 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 230000019612 pigmentation Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 150000004804 polysaccharides Chemical class 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000013772 propylene glycol Nutrition 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000011514 reflex Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000002271 resection Methods 0.000 description 2
- 229960000425 rizatriptan Drugs 0.000 description 2
- TXHZXHICDBAVJW-UHFFFAOYSA-N rizatriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1CN1C=NC=N1 TXHZXHICDBAVJW-UHFFFAOYSA-N 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 201000001197 subcortical band heterotopia Diseases 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229960003708 sumatriptan Drugs 0.000 description 2
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 201000008914 temporal lobe epilepsy Diseases 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- 238000011285 therapeutic regimen Methods 0.000 description 2
- 230000004797 therapeutic response Effects 0.000 description 2
- QAXBVGVYDCAVLV-UHFFFAOYSA-N tiletamine Chemical compound C=1C=CSC=1C1(NCC)CCCCC1=O QAXBVGVYDCAVLV-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000440 toxicity profile Toxicity 0.000 description 2
- 231100000820 toxicity test Toxicity 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 208000034373 type A muscular dystrophy-dystroglycanopathy Diseases 0.000 description 2
- 229960001130 urapidil Drugs 0.000 description 2
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 2
- 229960000604 valproic acid Drugs 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 229960004688 venlafaxine Drugs 0.000 description 2
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 229960000607 ziprasidone Drugs 0.000 description 2
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 2
- 229960001360 zolmitriptan Drugs 0.000 description 2
- UTAZCRNOSWWEFR-ZDUSSCGKSA-N zolmitriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1C[C@H]1COC(=O)N1 UTAZCRNOSWWEFR-ZDUSSCGKSA-N 0.000 description 2
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
- YQGDEPYYFWUPGO-VKHMYHEASA-N (3s)-4-azaniumyl-3-hydroxybutanoate Chemical compound [NH3+]C[C@@H](O)CC([O-])=O YQGDEPYYFWUPGO-VKHMYHEASA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- IPANUAHQWFDVAG-BTJKTKAUSA-N (z)-4-hydroxy-4-oxobut-2-enoate;1-methyl-4-thioxanthen-9-ylidenepiperidin-1-ium Chemical compound OC(=O)\C=C/C(O)=O.C1CN(C)CCC1=C1C2=CC=CC=C2SC2=CC=CC=C21 IPANUAHQWFDVAG-BTJKTKAUSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- BGMZUEKZENQUJY-UHFFFAOYSA-N 2-(4-iodo-2,5-dimethoxyphenyl)-1-methylethylamine Chemical compound COC1=CC(CC(C)N)=C(OC)C=C1I BGMZUEKZENQUJY-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- BBAZDLONIUABKI-UHFFFAOYSA-N 3-(2,4-dichlorophenoxy)-n-methyl-n-prop-2-ynylpropan-1-amine;hydrochloride Chemical compound Cl.C#CCN(C)CCCOC1=CC=C(Cl)C=C1Cl BBAZDLONIUABKI-UHFFFAOYSA-N 0.000 description 1
- APWHJJLFCMBWQT-UHFFFAOYSA-N 3-methoxy-n-[3-(2-methylpyrazol-3-yl)-4-(2-morpholin-4-ium-4-ylethoxy)phenyl]benzamide;chloride Chemical compound [Cl-].COC1=CC=CC(C(=O)NC=2C=C(C(OCC[NH+]3CCOCC3)=CC=2)C=2N(N=CC=2)C)=C1 APWHJJLFCMBWQT-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
- 229940116892 5 Hydroxytryptamine 2B receptor antagonist Drugs 0.000 description 1
- 101150096316 5 gene Proteins 0.000 description 1
- 102100024956 5-hydroxytryptamine receptor 2B Human genes 0.000 description 1
- 101710138092 5-hydroxytryptamine receptor 2B Proteins 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 108050008874 Annexin Proteins 0.000 description 1
- 102000000412 Annexin Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 206010003628 Atonic seizures Diseases 0.000 description 1
- 241001106067 Atropa Species 0.000 description 1
- 101150035467 BDNF gene Proteins 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 102100026548 Caspase-8 Human genes 0.000 description 1
- 108091005462 Cation channels Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010056467 Cerebral dysgenesis Diseases 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 208000031976 Channelopathies Diseases 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 201000001913 Childhood absence epilepsy Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 108050001175 Connexin Proteins 0.000 description 1
- 102000010970 Connexin Human genes 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 101100329834 Danio rerio gja1 gene Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 108700039964 Duplicate Genes Proteins 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013974 Dyspnoea paroxysmal nocturnal Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000024658 Epilepsy syndrome Diseases 0.000 description 1
- 208000002877 Epileptic Syndromes Diseases 0.000 description 1
- 101000706102 Esox lucius Parvalbumin alpha Proteins 0.000 description 1
- 102000004300 GABA-A Receptors Human genes 0.000 description 1
- 108090000839 GABA-A Receptors Proteins 0.000 description 1
- 101001105542 Gallus gallus Parvalbumin, thymic CPV3 Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 208000034308 Grand mal convulsion Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 101000684826 Homo sapiens Sodium channel protein type 2 subunit alpha Proteins 0.000 description 1
- 101000684820 Homo sapiens Sodium channel protein type 3 subunit alpha Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010070511 Hypoxic-ischaemic encephalopathy Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 206010022562 Intermittent claudication Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 208000005870 Lafora disease Diseases 0.000 description 1
- 206010048911 Lissencephaly Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108010008364 Melanocortins Proteins 0.000 description 1
- 102000006890 Methyl-CpG-Binding Protein 2 Human genes 0.000 description 1
- 108010072388 Methyl-CpG-Binding Protein 2 Proteins 0.000 description 1
- 229940091512 Monoamine oxidase A inhibitor Drugs 0.000 description 1
- 208000016119 Myoclonic epilepsy of infancy Diseases 0.000 description 1
- JNNOSTQEZICQQP-UHFFFAOYSA-N N-desmethylclozapine Chemical compound N=1C2=CC(Cl)=CC=C2NC2=CC=CC=C2C=1N1CCNCC1 JNNOSTQEZICQQP-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- COSPVUFTLGQDQL-UHFFFAOYSA-N Nelotanserin Chemical compound C1=C(C=2N(N=CC=2Br)C)C(OC)=CC=C1NC(=O)NC1=CC=C(F)C=C1F COSPVUFTLGQDQL-UHFFFAOYSA-N 0.000 description 1
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- FUHDRUMGQAGGCB-UHFFFAOYSA-N OC(=O)C(O)C(O)C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C Chemical compound OC(=O)C(O)C(O)C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C FUHDRUMGQAGGCB-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241001069925 Orestes Species 0.000 description 1
- 206010031123 Orthopnoea Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 101150084044 P gene Proteins 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 208000004327 Paroxysmal Dyspnea Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010034759 Petit mal epilepsy Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 206010036312 Post-traumatic epilepsy Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 208000006289 Rett Syndrome Diseases 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- 101150020107 SCN8A gene Proteins 0.000 description 1
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 102100023150 Sodium channel protein type 2 subunit alpha Human genes 0.000 description 1
- 102100023720 Sodium channel protein type 3 subunit alpha Human genes 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 102000005890 Spectrin Human genes 0.000 description 1
- 108010019965 Spectrin Proteins 0.000 description 1
- 101000783611 Takifugu rubripes 5-hydroxytryptamine receptor 1D Proteins 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 206010043994 Tonic convulsion Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 102000012275 Ubiquitin domains Human genes 0.000 description 1
- 108050002897 Ubiquitin domains Proteins 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
- MPBCKKVERDTCEL-LURJTMIESA-N [(7r)-3-bromo-2,5-dimethoxy-7-bicyclo[4.2.0]octa-1(6),2,4-trienyl]methanamine Chemical compound COC1=CC(Br)=C(OC)C2=C1[C@H](CN)C2 MPBCKKVERDTCEL-LURJTMIESA-N 0.000 description 1
- XQAXGZLFSSPBMK-UHFFFAOYSA-M [7-(dimethylamino)phenothiazin-3-ylidene]-dimethylazanium;chloride;trihydrate Chemical compound O.O.O.[Cl-].C1=CC(=[N+](C)C)C=C2SC3=CC(N(C)C)=CC=C3N=C21 XQAXGZLFSSPBMK-UHFFFAOYSA-M 0.000 description 1
- 206010000269 abscess Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000036982 action potential Effects 0.000 description 1
- 208000015150 agyria-pachygyria type 1 Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 229940125516 allosteric modulator Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229960002298 aminohydroxybutyric acid Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 208000029560 autism spectrum disease Diseases 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 229960005200 beclamide Drugs 0.000 description 1
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- GKPMEGXMKPQRTN-CBDIPHIASA-N benzylpenicillin clemizole Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1.C1=CC(Cl)=CC=C1CN1C2=CC=CC=C2N=C1C[NH+]1CCCC1 GKPMEGXMKPQRTN-CBDIPHIASA-N 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000007698 birth defect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 208000009973 brain hypoxia - ischemia Diseases 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 1
- AURFZBICLPNKBZ-SYBPFIFISA-N brexanolone Chemical compound C([C@@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 AURFZBICLPNKBZ-SYBPFIFISA-N 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- ZEWYCNBZMPELPF-UHFFFAOYSA-J calcium;potassium;sodium;2-hydroxypropanoic acid;sodium;tetrachloride Chemical compound [Na].[Na+].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[Ca+2].CC(O)C(O)=O ZEWYCNBZMPELPF-UHFFFAOYSA-J 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 206010008129 cerebral palsy Diseases 0.000 description 1
- 201000008191 cerebritis Diseases 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229960001448 chloropyramine Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960005132 cisapride Drugs 0.000 description 1
- DCSUBABJRXZOMT-UHFFFAOYSA-N cisapride Natural products C1CC(NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)C(OC)CN1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-UHFFFAOYSA-N 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 208000024980 claudication Diseases 0.000 description 1
- 229940110017 clemizolpenicillin Drugs 0.000 description 1
- 208000028502 clonic seizure Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 238000007418 data mining Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 235000021045 dietary change Nutrition 0.000 description 1
- 235000020930 dietary requirements Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000005584 early death Effects 0.000 description 1
- 230000000792 effect on seizure Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 208000028329 epileptic seizure Diseases 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 229960004979 fampridine Drugs 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 210000003976 gap junction Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000005176 gastrointestinal motility Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 201000008186 generalized epilepsy with febrile seizures plus Diseases 0.000 description 1
- 208000028326 generalized seizure Diseases 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 208000018578 heart valve disease Diseases 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 102000049589 human SCN1A Human genes 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 208000015210 hypertensive heart disease Diseases 0.000 description 1
- 230000001709 ictal effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 230000003585 interneuronal effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000010978 jasper Substances 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 208000014817 lissencephaly spectrum disease Diseases 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 235000015263 low fat diet Nutrition 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- FQQIIPAOSKSOJM-UHFFFAOYSA-N mebhydrolin Chemical compound C1N(C)CCC2=C1C1=CC=CC=C1N2CC1=CC=CC=C1 FQQIIPAOSKSOJM-UHFFFAOYSA-N 0.000 description 1
- 229960004934 mebhydrolin Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002865 melanocortin Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 238000012737 microarray-based gene expression Methods 0.000 description 1
- BYJYIKWMABSTKJ-ZNYNAASMSA-N migril Chemical compound Cl.OC(=O)[C@H](O)[C@@H](O)C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C1CN(C)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1.C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C=3C=CC=C4NC=C(C=34)C2)=C1)C)C1=CC=CC=C1.C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@@](C(N21)=O)(C)NC(=O)[C@H]1CN([C@H]2C(C=3C=CC=C4NC=C(C=34)C2)=C1)C)C1=CC=CC=C1 BYJYIKWMABSTKJ-ZNYNAASMSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000007479 molecular analysis Methods 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 208000028492 myoclonic seizure Diseases 0.000 description 1
- VEYWWAGBHABATA-UHFFFAOYSA-N n'-[(4-chlorophenyl)methyl]-n,n-dimethyl-n'-pyridin-2-ylethane-1,2-diamine;hydron;chloride Chemical compound [Cl-].C=1C=CC=NC=1N(CC[NH+](C)C)CC1=CC=C(Cl)C=C1 VEYWWAGBHABATA-UHFFFAOYSA-N 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 description 1
- 229960005254 naratriptan Drugs 0.000 description 1
- UNHGSHHVDNGCFN-UHFFFAOYSA-N naratriptan Chemical compound C=12[CH]C(CCS(=O)(=O)NC)=CC=C2N=CC=1C1CCN(C)CC1 UNHGSHHVDNGCFN-UHFFFAOYSA-N 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 229960002441 nefazodone hydrochloride Drugs 0.000 description 1
- DYCKFEBIOUQECE-UHFFFAOYSA-N nefazodone hydrochloride Chemical compound [H+].[Cl-].O=C1N(CCOC=2C=CC=CC=2)C(CC)=NN1CCCN(CC1)CCN1C1=CC=CC(Cl)=C1 DYCKFEBIOUQECE-UHFFFAOYSA-N 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 229950006103 nelotanserin Drugs 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000008587 neuronal excitability Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
- 201000006352 oculocerebrorenal syndrome Diseases 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940016084 oleptro Drugs 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 208000012144 orthopnea Diseases 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 208000033300 perinatal asphyxia Diseases 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000012660 pharmacological inhibitor Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229960001416 pilocarpine Drugs 0.000 description 1
- 229960000399 pimethixene Drugs 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 230000000270 postfertilization Effects 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003405 preventing effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000216 proconvulsive effect Effects 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 201000001204 progressive myoclonus epilepsy Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 230000001179 pupillary effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000012113 quantitative test Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 101150043066 scn4aa gene Proteins 0.000 description 1
- 101150070019 scn4ab gene Proteins 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 230000009154 spontaneous behavior Effects 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 230000033912 thigmotaxis Effects 0.000 description 1
- 229960004523 tiletamine Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 208000028500 tonic seizure Diseases 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000006208 topical dosage form Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 231100000583 toxicological profile Toxicity 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical class C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 1
- 208000009999 tuberous sclerosis Diseases 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-M undecanoate Chemical compound CCCCCCCCCCC([O-])=O ZDPHROOEEOARMN-UHFFFAOYSA-M 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 229960003474 ziprasidone hydrochloride Drugs 0.000 description 1
- ZCBZSCBNOOIHFP-UHFFFAOYSA-N ziprasidone hydrochloride hydrate Chemical compound [H+].O.[Cl-].C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 ZCBZSCBNOOIHFP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562120726P | 2015-02-25 | 2015-02-25 | |
| PCT/US2016/019368 WO2016138138A1 (en) | 2015-02-25 | 2016-02-24 | 5ht agonists for treating disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2920886T3 true ES2920886T3 (es) | 2022-08-11 |
Family
ID=56789223
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16756282T Active ES2920886T3 (es) | 2015-02-25 | 2016-02-24 | Agonistas de 5HT para el tratamiento de trastornos epilépticos |
Country Status (21)
| Country | Link |
|---|---|
| US (4) | US10874643B2 (enExample) |
| EP (3) | EP3632434A1 (enExample) |
| JP (5) | JP6884703B2 (enExample) |
| KR (3) | KR102385665B1 (enExample) |
| CN (2) | CN113546174A (enExample) |
| AU (3) | AU2016222804C1 (enExample) |
| BR (1) | BR112017018297B1 (enExample) |
| CA (2) | CA3204599A1 (enExample) |
| CY (1) | CY1125360T1 (enExample) |
| DK (1) | DK3261640T3 (enExample) |
| EA (2) | EA201791882A1 (enExample) |
| ES (1) | ES2920886T3 (enExample) |
| HR (1) | HRP20220822T1 (enExample) |
| HU (1) | HUE059559T2 (enExample) |
| LT (1) | LT3261640T (enExample) |
| PL (1) | PL3261640T3 (enExample) |
| PT (1) | PT3261640T (enExample) |
| RS (1) | RS63426B1 (enExample) |
| SI (1) | SI3261640T1 (enExample) |
| SM (1) | SMT202200276T1 (enExample) |
| WO (1) | WO2016138138A1 (enExample) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9549909B2 (en) | 2013-05-03 | 2017-01-24 | The Katholieke Universiteit Leuven | Method for the treatment of dravet syndrome |
| EP3632434A1 (en) | 2015-02-25 | 2020-04-08 | The Regents of the University of California | The 5ht agonist clemizole for use in treating disorders |
| GB201620095D0 (en) * | 2016-11-28 | 2017-01-11 | Terali Innov Sas And Univ De Strasbourg And Inserm (Inst Nat De La Sante Et De La Rech Medicale) And | Novel use |
| US20170174614A1 (en) | 2015-12-22 | 2017-06-22 | Zogenix International Limited | Metabolism resistant fenfluramine analogs and methods of using the same |
| CN108883399B (zh) | 2015-12-22 | 2021-06-22 | 周格尼克斯国际有限公司 | 芬氟拉明组合物及其制备方法 |
| RU2021106383A (ru) | 2016-08-24 | 2021-04-05 | Зодженикс Интернэшнл Лимитед | Состав для ингибирования образования агонистов 5-ht2b и способы его применения |
| WO2018115001A1 (en) | 2016-12-20 | 2018-06-28 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
| RU2764443C2 (ru) | 2016-12-20 | 2022-01-17 | Лтс Ломанн Терапи-Систем Аг | Трансдермальная терапевтическая система, содержащая азенапин и полисилоксан или полиизобутилен |
| CN110799180A (zh) | 2017-06-26 | 2020-02-14 | 罗曼治疗系统股份公司 | 含阿塞那平和硅氧烷丙烯酸杂化聚合物的经皮治疗系统 |
| US10682317B2 (en) * | 2017-09-26 | 2020-06-16 | Zogenix International Limited | Ketogenic diet compatible fenfluramine formulation |
| WO2019216919A1 (en) | 2018-05-11 | 2019-11-14 | Zogenix International Limited | Compositions and methods for treating seizure-induced sudden death |
| EP3806835A1 (en) | 2018-06-14 | 2021-04-21 | Zogenix International Limited | Compositions and methods for treating respiratory depression with fenfluramine |
| CN112533593A (zh) | 2018-06-20 | 2021-03-19 | 罗曼治疗系统股份公司 | 含有阿塞那平的透皮治疗系统 |
| AU2019291060B2 (en) | 2018-06-20 | 2024-09-05 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
| WO2020018839A1 (en) | 2018-07-18 | 2020-01-23 | The Regents Of The University Of California | Compounds and methods for synergistic activation of m channels |
| CN112930175A (zh) * | 2018-07-27 | 2021-06-08 | 泽农医药公司 | 治疗癫痫的方法 |
| US12144787B2 (en) | 2018-11-19 | 2024-11-19 | Zogenix International Limited | Method of treating patients with a mutation in cyclin-dependent kinase-like 5 (CDKL5) |
| KR20220015413A (ko) * | 2019-05-29 | 2022-02-08 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 간질을 치료하기 위한 방법 및 조성물 |
| EP3791873A1 (en) * | 2019-09-16 | 2021-03-17 | Universite De Bordeaux | Methods of treatment and/or prevention of disorders and symptoms related to bkca and/or sk channelophathies |
| US20230020036A1 (en) * | 2019-10-23 | 2023-01-19 | Neurocycle Therapeutics, Inc. | Treatment of epileptic conditions with gabaa receptor modulators |
| IL292367A (en) * | 2019-10-23 | 2022-06-01 | Maplight Therapeutics Inc | Methods for treating the symptoms of autism spectrum disorder |
| KR20210054684A (ko) | 2019-11-06 | 2021-05-14 | 동국대학교 경주캠퍼스 산학협력단 | 라미나린을 유효성분으로 함유하는 허혈성 뇌혈관 질환 예방용 조성물 |
| IL293525A (en) * | 2019-12-06 | 2022-08-01 | Marinus Pharmaceuticals Inc | Ganaxolone for use in the treatment of multiple sclerosis complex |
| KR102476771B1 (ko) * | 2020-05-08 | 2022-12-13 | 광운대학교 산학협력단 | 뇌질환 검증용 eeg 바이오 마커 분석 알고리즘을 통하여 소아 뇌전증 환자 미주신경자극술 효과를 예측하는 방법 |
| US11612574B2 (en) | 2020-07-17 | 2023-03-28 | Zogenix International Limited | Method of treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) |
| JP2024512069A (ja) * | 2021-03-25 | 2024-03-18 | マップライト セラピューティクス，インコーポレイテッド | ゾルミトリプタンを含む医薬組成物 |
| EP4346804A4 (en) * | 2021-06-01 | 2025-05-07 | Arena Pharmaceuticals, Inc. | TREATMENT PROCEDURES |
| WO2022261400A1 (en) * | 2021-06-10 | 2022-12-15 | Neurelis, Inc. | Methods and compositions for treating seizure disorders in pediatric patients |
| CA3227492A1 (en) * | 2021-07-30 | 2023-02-02 | Hahn-Jun Lee | Clemizole formulation |
| WO2023107965A1 (en) * | 2021-12-06 | 2023-06-15 | Terran Biosciences, Inc. | Salt and solid forms of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (dom), 2,5-dimethoxy-4-iodoamphetamine (doi), 2,5-dimethoxy-4-bromoamphetamine (dob), and 2,5-dimethoxy-4-chloroamphetamine (doc) |
| WO2023144166A1 (en) | 2022-01-26 | 2023-08-03 | Neurolixis | Use of serotonin 5-ht1a receptor agonists to treat diseases associated with sudden unexpected death in epilepsy |
| US11974992B2 (en) | 2022-01-26 | 2024-05-07 | Neurolixis | Use of serotonin 5-HT1A receptor agonists to treat diseases associated with sudden unexpected death in epilepsy |
| US20250295611A1 (en) * | 2022-04-27 | 2025-09-25 | Tessellate Therapeutics Inc. | Methods of treating 5ht2a receptor-mediated conditions |
| WO2024118280A1 (en) * | 2022-11-30 | 2024-06-06 | Mind Medicine, Inc. | 4-alkenyl and 4-alkynyl phenethylamine derivatives and related compounds with modified dom-like action |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2436883C2 (de) | 1974-07-29 | 1985-08-22 | Schering AG, 1000 Berlin und 4709 Bergkamen | Benzimidazol-Derivate, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
| US4911920A (en) | 1986-07-30 | 1990-03-27 | Alcon Laboratories, Inc. | Sustained release, comfort formulation for glaucoma therapy |
| FR2588189B1 (fr) | 1985-10-03 | 1988-12-02 | Merck Sharp & Dohme | Composition pharmaceutique de type a transition de phase liquide-gel |
| DK0495421T3 (da) | 1991-01-15 | 1996-12-09 | Alcon Lab Inc | Anvendelse af carragenaner i topiske ophthalmiske sammensætninger |
| US5212162A (en) | 1991-03-27 | 1993-05-18 | Alcon Laboratories, Inc. | Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions |
| US6309853B1 (en) | 1994-08-17 | 2001-10-30 | The Rockfeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
| US6323237B1 (en) | 1997-03-17 | 2001-11-27 | Btg International Limited | Therapeutic compositions |
| GB9927844D0 (en) * | 1999-11-26 | 2000-01-26 | Glaxo Group Ltd | Chemical compounds |
| US7326536B2 (en) | 2001-05-03 | 2008-02-05 | Eli Lilly And Company | Agents for treatment of HCV and methods of use |
| US6559293B1 (en) | 2002-02-15 | 2003-05-06 | Transform Pharmaceuticals, Inc. | Topiramate sodium trihydrate |
| US7582428B2 (en) | 2003-08-22 | 2009-09-01 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for identifying anti-HCV agents |
| US20050215589A1 (en) | 2003-09-03 | 2005-09-29 | Roger Crossley | Inhibitors of 5-HT2A receptor |
| EP1787679A1 (en) * | 2005-07-29 | 2007-05-23 | Laboratorios Del Dr. Esteve, S.A. | Use of compounds binding to the sigma receptor for the treatment of diabetes-associated pain |
| US7635710B2 (en) | 2006-02-15 | 2009-12-22 | Neurim Pharmaceuticals (1991) Ltd. | Pyrone-indole derivatives and process for their preparation |
| BRPI0716604A2 (pt) | 2006-09-08 | 2013-04-09 | Braincells Inc | combinaÇÕes contendo um derivado de 4-acilaminopiridina |
| WO2008036586A2 (en) | 2006-09-20 | 2008-03-27 | Waters Investments Limited | Apparatus and methods of fluid chromatography |
| CN101652259B (zh) | 2007-04-06 | 2012-07-11 | 皇家飞利浦电子股份有限公司 | 空气污染传感器系统 |
| WO2008133884A2 (en) * | 2007-04-23 | 2008-11-06 | Combinatorx, Incorporated | Methods and compositions for the treatment of neurodegenerative disorders |
| US20110009351A1 (en) | 2007-05-09 | 2011-01-13 | Traffick Therepeutics Inc. | Screening assay to identify correctors of protein trafficking defects |
| TW200927102A (en) * | 2007-09-18 | 2009-07-01 | Univ Stanford | Methods of treating a flaviviridae family viral infection, compositions for treating a flaviviridae family viral infection, and screening assays for identifying compositions for treating a flaviviridae family viral infection |
| KR100925176B1 (ko) | 2007-09-21 | 2009-11-05 | 한국전자통신연구원 | 지리 정보를 이용한 네트워크 상태 표시장치 및 방법 |
| CA2715192A1 (en) | 2008-02-19 | 2009-08-27 | Adolor Corporation | Beloxepin, its enantiomers, and analogs thereof for the treatment of pain |
| WO2009128907A1 (en) | 2008-04-16 | 2009-10-22 | Arena Pharmaceuticals, Inc. | Processes useful for the synthesis of (r)-1-{2-[4'-(3-methoxypropane-1-sulfonyl)-biphenyl-4-yl]-ethyl}-2-methyl-pyrrolidine |
| DK2307035T3 (da) | 2008-05-16 | 2014-01-20 | Nono Inc | Anvendelse af en PSD-95 inhibitor ved behandlingen af epilepsi |
| US20110217265A1 (en) | 2008-09-23 | 2011-09-08 | Glenn Jeffrey S | Screening for Inhibitors of HCV Amphipathic Helix (AH) Function |
| JP2012520884A (ja) | 2009-03-18 | 2012-09-10 | ザ ボード オブ トラスティーズ オブ ザ リランド スタンフォード ジュニア ユニバーシティー | フラビウイルス科ウイルス感染症を治療する方法および組成物 |
| JP2012520885A (ja) | 2009-03-18 | 2012-09-10 | ザ ボード オブ トラスティーズ オブ ザ リランド スタンフォード ジュニア ユニバーシティー | フラビウイルス科ウイルス感染症を治療する方法および組成物 |
| CA2760219C (en) | 2009-05-13 | 2016-08-16 | Nektar Therapeutics | Oligomer-containing substituted aromatic triazine compounds |
| CN102666537A (zh) | 2009-10-20 | 2012-09-12 | 艾格尔生物制药股份有限公司 | 治疗黄病毒科病毒感染的氮杂吲唑 |
| WO2014123909A1 (en) | 2013-02-05 | 2014-08-14 | University Of Washington Through Its Center For Commercialization | Positive allosteric modulators of the gaba-a receptor in the treatment of autism |
| US9549909B2 (en) * | 2013-05-03 | 2017-01-24 | The Katholieke Universiteit Leuven | Method for the treatment of dravet syndrome |
| WO2015026849A1 (en) * | 2013-08-19 | 2015-02-26 | The Regents Of The University Of California | Compounds and methods for treating an epileptic disorder |
| WO2015066344A1 (en) * | 2013-11-01 | 2015-05-07 | Arena Pharmaceuticals, Inc. | 5-ht2c receptor agonists and compositions and methods of use |
| CN104936947B (zh) | 2013-12-27 | 2017-03-08 | 杭州普晒医药科技有限公司 | 氯卡色林盐及其晶体、其制备方法和用途 |
| EP3632434A1 (en) | 2015-02-25 | 2020-04-08 | The Regents of the University of California | The 5ht agonist clemizole for use in treating disorders |
| GB2539472A (en) | 2015-06-17 | 2016-12-21 | Gw Res Ltd | Use of cannabinoids in the treatment of epilepsy |
-
2016
- 2016-02-24 EP EP19211183.9A patent/EP3632434A1/en not_active Withdrawn
- 2016-02-24 EA EA201791882A patent/EA201791882A1/ru unknown
- 2016-02-24 CN CN202111041649.4A patent/CN113546174A/zh active Pending
- 2016-02-24 BR BR112017018297-1A patent/BR112017018297B1/pt active IP Right Grant
- 2016-02-24 SM SM20220276T patent/SMT202200276T1/it unknown
- 2016-02-24 EP EP16756282.6A patent/EP3261640B1/en active Active
- 2016-02-24 RS RS20220598A patent/RS63426B1/sr unknown
- 2016-02-24 AU AU2016222804A patent/AU2016222804C1/en active Active
- 2016-02-24 KR KR1020177026528A patent/KR102385665B1/ko active Active
- 2016-02-24 WO PCT/US2016/019368 patent/WO2016138138A1/en not_active Ceased
- 2016-02-24 LT LTEPPCT/US2016/019368T patent/LT3261640T/lt unknown
- 2016-02-24 US US15/552,784 patent/US10874643B2/en active Active
- 2016-02-24 HU HUE16756282A patent/HUE059559T2/hu unknown
- 2016-02-24 CA CA3204599A patent/CA3204599A1/en active Pending
- 2016-02-24 DK DK16756282.6T patent/DK3261640T3/da active
- 2016-02-24 CA CA2977135A patent/CA2977135C/en active Active
- 2016-02-24 EP EP22157142.5A patent/EP4043016B1/en active Active
- 2016-02-24 EA EA201992474A patent/EA201992474A3/ru unknown
- 2016-02-24 ES ES16756282T patent/ES2920886T3/es active Active
- 2016-02-24 CN CN201680023991.2A patent/CN107530326B/zh active Active
- 2016-02-24 JP JP2017544887A patent/JP6884703B2/ja active Active
- 2016-02-24 HR HRP20220822TT patent/HRP20220822T1/hr unknown
- 2016-02-24 KR KR1020227011498A patent/KR20220048045A/ko not_active Ceased
- 2016-02-24 PT PT167562826T patent/PT3261640T/pt unknown
- 2016-02-24 PL PL16756282.6T patent/PL3261640T3/pl unknown
- 2016-02-24 KR KR1020237037303A patent/KR20230152844A/ko active Pending
- 2016-02-24 SI SI201631545T patent/SI3261640T1/sl unknown
-
2019
- 2019-11-08 US US16/679,112 patent/US11648237B2/en active Active
-
2020
- 2020-05-01 JP JP2020081127A patent/JP2020143087A/ja active Pending
- 2020-10-28 US US17/082,929 patent/US20210154171A1/en active Pending
-
2021
- 2021-06-23 AU AU2021204261A patent/AU2021204261B2/en active Active
- 2021-08-05 JP JP2021128790A patent/JP2021185148A/ja active Pending
-
2022
- 2022-05-16 AU AU2022203274A patent/AU2022203274B2/en active Active
- 2022-06-06 JP JP2022091363A patent/JP2022116307A/ja active Pending
- 2022-06-22 CY CY20221100428T patent/CY1125360T1/el unknown
-
2023
- 2023-03-30 US US18/192,955 patent/US12447144B2/en active Active
- 2023-09-29 JP JP2023169390A patent/JP2024009839A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2920886T3 (es) | Agonistas de 5HT para el tratamiento de trastornos epilépticos | |
| US20230372304A1 (en) | Compounds and methods for treating an epileptic disorder | |
| HK40079848A (en) | The 5ht agonist clemizole for use in treating epilepsy disorders | |
| EA046651B1 (ru) | Агонисты 5ht для лечения нарушений | |
| EA040818B1 (ru) | Способ лечения эпилептического расстройства с помощью агониста рецептора 5ht |