ES2988130T3 - Método para el tratamiento de epilepsia - Google Patents

Info

Publication number

ES2988130T3

ES2988130T3 ES19750214T ES19750214T ES2988130T3 ES 2988130 T3 ES2988130 T3 ES 2988130T3 ES 19750214 T ES19750214 T ES 19750214T ES 19750214 T ES19750214 T ES 19750214T ES 2988130 T3 ES2988130 T3 ES 2988130T3

Authority

ES

Spain

Prior art keywords

compound

norfenfluramine

fenfluramine

epilepsy

seizure

Prior art date

2018-07-27

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

• Espacenet
• Global Dossier
• Discuss

• 206010015037 epilepsy Diseases 0.000 title claims abstract description 102
• 238000011282 treatment Methods 0.000 title claims abstract description 38
• 238000000034 method Methods 0.000 title abstract description 41
• 206010010904 Convulsion Diseases 0.000 claims abstract description 185
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 54
• 208000028329 epileptic seizure Diseases 0.000 claims abstract description 40
• 208000036572 Myoclonic epilepsy Diseases 0.000 claims abstract description 26
• 201000007547 Dravet syndrome Diseases 0.000 claims abstract description 25
• 206010073677 Severe myoclonic epilepsy of infancy Diseases 0.000 claims abstract description 25
• 150000001875 compounds Chemical class 0.000 claims description 157
• MLBHFBKZUPLWBD-SSDOTTSWSA-N (2R)-1-[3-(trifluoromethyl)phenyl]-2-propanamine Chemical compound C[C@@H](N)CC1=CC=CC(C(F)(F)F)=C1 MLBHFBKZUPLWBD-SSDOTTSWSA-N 0.000 claims description 50
• 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 claims description 39
• 150000003839 salts Chemical class 0.000 claims description 35
• 239000003814 drug Substances 0.000 claims description 33
• DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 claims description 11
• 201000006792 Lennox-Gastaut syndrome Diseases 0.000 claims description 7
• 229960003562 phentermine Drugs 0.000 claims description 5
• 239000001961 anticonvulsive agent Substances 0.000 abstract description 68
• DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical class CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 abstract description 46
• 229960003965 antiepileptics Drugs 0.000 abstract description 43
• 230000001773 anti-convulsant effect Effects 0.000 abstract description 18
• 241000124008 Mammalia Species 0.000 abstract description 16
• 230000001451 cardiotoxic effect Effects 0.000 abstract description 4
• 231100000457 cardiotoxic Toxicity 0.000 abstract 1
• 238000012360 testing method Methods 0.000 description 71
• 239000000203 mixture Substances 0.000 description 61
• 229960001582 fenfluramine Drugs 0.000 description 55
• 208000035475 disorder Diseases 0.000 description 45
• 230000000694 effects Effects 0.000 description 45
• 241000699670 Mus sp. Species 0.000 description 41
• 239000008194 pharmaceutical composition Substances 0.000 description 40
• 241001465754 Metazoa Species 0.000 description 38
• 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 26
• DBGIVFWFUFKIQN-SECBINFHSA-N Levofenfluramine Chemical compound CCN[C@H](C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-SECBINFHSA-N 0.000 description 26
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
• 241000699666 Mus <mouse, genus> Species 0.000 description 23
• 238000002360 preparation method Methods 0.000 description 20
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
• 239000003981 vehicle Substances 0.000 description 19
• MLBHFBKZUPLWBD-ZETCQYMHSA-N (2S)-1-[3-(trifluoromethyl)phenyl]-2-propanamine Chemical compound C[C@H](N)CC1=CC=CC(C(F)(F)F)=C1 MLBHFBKZUPLWBD-ZETCQYMHSA-N 0.000 description 18
• -1 3H and carbon-14 Chemical compound 0.000 description 18
• 241000700159 Rattus Species 0.000 description 18
• 229940079593 drug Drugs 0.000 description 17
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
• 239000000546 pharmaceutical excipient Substances 0.000 description 16
• 239000000126 substance Substances 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• 239000007788 liquid Substances 0.000 description 15
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 14
• 239000000243 solution Substances 0.000 description 14
• 230000001965 increasing effect Effects 0.000 description 13
• 229940002612 prodrug Drugs 0.000 description 13
• 239000000651 prodrug Substances 0.000 description 13
• DBGIVFWFUFKIQN-VIFPVBQESA-N (+)-Fenfluramine Chemical compound CCN[C@@H](C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-VIFPVBQESA-N 0.000 description 12
• 206010009346 Clonus Diseases 0.000 description 12
• 230000006698 induction Effects 0.000 description 12
• 230000000638 stimulation Effects 0.000 description 12
• 241000282412 Homo Species 0.000 description 11
• 238000003556 assay Methods 0.000 description 11
• 230000006399 behavior Effects 0.000 description 11
• 229960004597 dexfenfluramine Drugs 0.000 description 11
• 238000001727 in vivo Methods 0.000 description 11
• 239000007924 injection Substances 0.000 description 11
• 238000002347 injection Methods 0.000 description 11
• 239000011780 sodium chloride Substances 0.000 description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
• 206010061334 Partial seizures Diseases 0.000 description 10
• 239000003085 diluting agent Substances 0.000 description 10
• 239000002207 metabolite Substances 0.000 description 10
• 239000007787 solid Substances 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 238000011765 DBA/2 mouse Methods 0.000 description 9
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
• 101150022529 Scn1a gene Proteins 0.000 description 9
• 239000004480 active ingredient Substances 0.000 description 9
• 229960001264 benfluorex Drugs 0.000 description 9
• CJAVTWRYCDNHSM-UHFFFAOYSA-N benzoic acid 2-[1-[3-(trifluoromethyl)phenyl]propan-2-ylamino]ethyl ester Chemical compound C=1C=CC=CC=1C(=O)OCCNC(C)CC1=CC=CC(C(F)(F)F)=C1 CJAVTWRYCDNHSM-UHFFFAOYSA-N 0.000 description 9
• 210000004556 brain Anatomy 0.000 description 9
• 230000001037 epileptic effect Effects 0.000 description 9
• 238000007912 intraperitoneal administration Methods 0.000 description 9
• 229940124597 therapeutic agent Drugs 0.000 description 9
• SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 8
• 241000252212 Danio rerio Species 0.000 description 8
• 239000000443 aerosol Substances 0.000 description 8
• 238000004458 analytical method Methods 0.000 description 8
• 238000009472 formulation Methods 0.000 description 8
• 229910052739 hydrogen Inorganic materials 0.000 description 8
• 239000001257 hydrogen Substances 0.000 description 8
• 229960002748 norepinephrine Drugs 0.000 description 8
• SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 8
• 230000003389 potentiating effect Effects 0.000 description 8
• 208000024255 Audiogenic seizures Diseases 0.000 description 7
• IYGYMKDQCDOMRE-QRWMCTBCSA-N Bicculine Chemical compound O([C@H]1C2C3=CC=4OCOC=4C=C3CCN2C)C(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-QRWMCTBCSA-N 0.000 description 7
• LHNKBXRFNPMIBR-UHFFFAOYSA-N Picrotoxin Natural products CC(C)(O)C1(O)C2OC(=O)C1C3(O)C4OC4C5C(=O)OC2C35C LHNKBXRFNPMIBR-UHFFFAOYSA-N 0.000 description 7
• 206010043994 Tonic convulsion Diseases 0.000 description 7
• 238000010171 animal model Methods 0.000 description 7
• 230000003542 behavioural effect Effects 0.000 description 7
• AACMFFIUYXGCOC-UHFFFAOYSA-N bicuculline Natural products CN1CCc2cc3OCOc3cc2C1C4OCc5c6OCOc6ccc45 AACMFFIUYXGCOC-UHFFFAOYSA-N 0.000 description 7
• 238000006243 chemical reaction Methods 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 230000002566 clonic effect Effects 0.000 description 7
• IYGYMKDQCDOMRE-UHFFFAOYSA-N d-Bicucullin Natural products CN1CCC2=CC=3OCOC=3C=C2C1C1OC(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-UHFFFAOYSA-N 0.000 description 7
• 230000034994 death Effects 0.000 description 7
• 231100000517 death Toxicity 0.000 description 7
• 239000003937 drug carrier Substances 0.000 description 7
• VJKUPQSHOVKBCO-AHMKVGDJSA-N picrotoxin Chemical compound O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(=C)C)[C@@H]1C(=O)O2.O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(C)(O)C)[C@@H]1C(=O)O2 VJKUPQSHOVKBCO-AHMKVGDJSA-N 0.000 description 7
• 230000001256 tonic effect Effects 0.000 description 7
• CJAVTWRYCDNHSM-CQSZACIVSA-N 2-[[(2r)-1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]ethyl benzoate Chemical compound C([C@@H](C)NCCOC(=O)C=1C=CC=CC=1)C1=CC=CC(C(F)(F)F)=C1 CJAVTWRYCDNHSM-CQSZACIVSA-N 0.000 description 6
• 208000014644 Brain disease Diseases 0.000 description 6
• 206010053398 Clonic convulsion Diseases 0.000 description 6
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
• 201000008009 Early infantile epileptic encephalopathy Diseases 0.000 description 6
• 208000032274 Encephalopathy Diseases 0.000 description 6
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
• 208000034308 Grand mal convulsion Diseases 0.000 description 6
• 208000035899 Infantile spasms syndrome Diseases 0.000 description 6
• 208000037012 Psychomotor seizures Diseases 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 239000000556 agonist Substances 0.000 description 6
• 239000005557 antagonist Substances 0.000 description 6
• 208000013257 developmental and epileptic encephalopathy Diseases 0.000 description 6
• 201000010099 disease Diseases 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• 210000003194 forelimb Anatomy 0.000 description 6
• 201000008186 generalized epilepsy with febrile seizures plus Diseases 0.000 description 6
• 229910052757 nitrogen Inorganic materials 0.000 description 6
• 230000002829 reductive effect Effects 0.000 description 6
• 201000005070 reflex epilepsy Diseases 0.000 description 6
• 230000004044 response Effects 0.000 description 6
• 206010048610 Cardiotoxicity Diseases 0.000 description 5
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
• 101000631760 Homo sapiens Sodium channel protein type 1 subunit alpha Proteins 0.000 description 5
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
• 102100028910 Sodium channel protein type 1 subunit alpha Human genes 0.000 description 5
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 5
• 208000003554 absence epilepsy Diseases 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• 231100000259 cardiotoxicity Toxicity 0.000 description 5
• 210000003169 central nervous system Anatomy 0.000 description 5
• 238000010790 dilution Methods 0.000 description 5
• 239000012895 dilution Substances 0.000 description 5
• 230000001747 exhibiting effect Effects 0.000 description 5
• 230000000670 limiting effect Effects 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 230000003287 optical effect Effects 0.000 description 5
• 239000000523 sample Substances 0.000 description 5
• 239000002399 serotonin 2A agonist Substances 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• 238000007920 subcutaneous administration Methods 0.000 description 5
• 239000004094 surface-active agent Substances 0.000 description 5
• 230000009182 swimming Effects 0.000 description 5
• 208000024891 symptom Diseases 0.000 description 5
• 238000001291 vacuum drying Methods 0.000 description 5
• CJAVTWRYCDNHSM-AWEZNQCLSA-N 2-[[(2s)-1-[3-(trifluoromethyl)phenyl]propan-2-yl]amino]ethyl benzoate Chemical compound C([C@H](C)NCCOC(=O)C=1C=CC=CC=1)C1=CC=CC(C(F)(F)F)=C1 CJAVTWRYCDNHSM-AWEZNQCLSA-N 0.000 description 4
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
• 206010070530 Benign rolandic epilepsy Diseases 0.000 description 4
• 208000016132 Epilepsy with myoclonic absences Diseases 0.000 description 4
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
• 206010020843 Hyperthermia Diseases 0.000 description 4
• 239000005909 Kieselgur Substances 0.000 description 4
• 206010028347 Muscle twitching Diseases 0.000 description 4
• 208000002033 Myoclonus Diseases 0.000 description 4
• 208000033063 Progressive myoclonic epilepsy Diseases 0.000 description 4
• 208000004974 Rolandic Epilepsy Diseases 0.000 description 4
• 239000002671 adjuvant Substances 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 201000008916 benign epilepsy with centrotemporal spikes Diseases 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 229910052799 carbon Inorganic materials 0.000 description 4
• 208000033205 childhood epilepsy with centrotemporal spikes Diseases 0.000 description 4
• 208000028502 clonic seizure Diseases 0.000 description 4
• 239000003086 colorant Substances 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 231100000673 dose–response relationship Toxicity 0.000 description 4
• 238000012377 drug delivery Methods 0.000 description 4
• 230000002526 effect on cardiovascular system Effects 0.000 description 4
• 238000002101 electrospray ionisation tandem mass spectrometry Methods 0.000 description 4
• 235000003599 food sweetener Nutrition 0.000 description 4
• 230000000971 hippocampal effect Effects 0.000 description 4
• 230000036031 hyperthermia Effects 0.000 description 4
• 230000006872 improvement Effects 0.000 description 4
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 4
• 238000002552 multiple reaction monitoring Methods 0.000 description 4
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
• 230000007170 pathology Effects 0.000 description 4
• 229920003229 poly(methyl methacrylate) Polymers 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• 239000004926 polymethyl methacrylate Substances 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 238000011160 research Methods 0.000 description 4
• 239000002485 serotonin 2C agonist Substances 0.000 description 4
• 230000002269 spontaneous effect Effects 0.000 description 4
• 239000003381 stabilizer Substances 0.000 description 4
• 239000003765 sweetening agent Substances 0.000 description 4
• 239000003826 tablet Substances 0.000 description 4
• 231100000419 toxicity Toxicity 0.000 description 4
• 230000001988 toxicity Effects 0.000 description 4
• 229910052722 tritium Inorganic materials 0.000 description 4
• 210000003135 vibrissae Anatomy 0.000 description 4
• BVJDPWSJTZGLTJ-KBPBESRZSA-N (2s)-n-[(1s)-1-phenylethyl]-1-[3-(trifluoromethyl)phenyl]propan-2-amine Chemical compound C([C@H](C)N[C@@H](C)C=1C=CC=CC=1)C1=CC=CC(C(F)(F)F)=C1 BVJDPWSJTZGLTJ-KBPBESRZSA-N 0.000 description 3
• 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 3
• 108010072584 5-HT2B Serotonin Receptor Proteins 0.000 description 3
• 102000006969 5-HT2B Serotonin Receptor Human genes 0.000 description 3
• 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 3
• 206010052075 Acquired epileptic aphasia Diseases 0.000 description 3
• 208000024827 Alzheimer disease Diseases 0.000 description 3
• 208000009575 Angelman syndrome Diseases 0.000 description 3
• 206010003591 Ataxia Diseases 0.000 description 3
• 206010003805 Autism Diseases 0.000 description 3
• 208000020706 Autistic disease Diseases 0.000 description 3
• 208000030169 Benign childhood occipital epilepsy, Panayiotopoulos type Diseases 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 208000013576 CDKL5 disease Diseases 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• 206010008748 Chorea Diseases 0.000 description 3
• GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 3
• 208000001654 Drug Resistant Epilepsy Diseases 0.000 description 3
• 206010071545 Early infantile epileptic encephalopathy with burst-suppression Diseases 0.000 description 3
• 238000000729 Fisher's exact test Methods 0.000 description 3
• 201000009010 Frontal lobe epilepsy Diseases 0.000 description 3
• 208000007686 GLUT1 deficiency syndrome Diseases 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
• 108700006771 Glut1 Deficiency Syndrome Proteins 0.000 description 3
• 101001072243 Homo sapiens Protocadherin-19 Proteins 0.000 description 3
• 206010021750 Infantile Spasms Diseases 0.000 description 3
• 201000008189 Juvenile absence epilepsy Diseases 0.000 description 3
• 206010071082 Juvenile myoclonic epilepsy Diseases 0.000 description 3
• 201000005802 Landau-Kleffner Syndrome Diseases 0.000 description 3
• 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 3
• 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 3
• 208000012902 Nervous system disease Diseases 0.000 description 3
• 208000032461 Panayiotopoulos type benign childhood occipital epilepsy Diseases 0.000 description 3
• 208000037158 Partial Epilepsies Diseases 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 102100036389 Protocadherin-19 Human genes 0.000 description 3
• 239000007868 Raney catalyst Substances 0.000 description 3
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
• 229910000564 Raney nickel Inorganic materials 0.000 description 3
• 206010071141 Rasmussen encephalitis Diseases 0.000 description 3
• 208000004160 Rasmussen subacute encephalitis Diseases 0.000 description 3
• 208000006289 Rett Syndrome Diseases 0.000 description 3
• 208000035208 Ring chromosome 20 syndrome Diseases 0.000 description 3
• 208000026911 Tuberous sclerosis complex Diseases 0.000 description 3
• 201000006791 West syndrome Diseases 0.000 description 3
• 208000027418 Wounds and injury Diseases 0.000 description 3
• 229960000583 acetic acid Drugs 0.000 description 3
• 230000002411 adverse Effects 0.000 description 3
• 230000003281 allosteric effect Effects 0.000 description 3
• 230000003556 anti-epileptic effect Effects 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• 229940049706 benzodiazepine Drugs 0.000 description 3
• 150000001557 benzodiazepines Chemical class 0.000 description 3
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 238000012512 characterization method Methods 0.000 description 3
• 238000000576 coating method Methods 0.000 description 3
• 208000015134 congenital hypothalamic hamartoma syndrome Diseases 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• 230000036461 convulsion Effects 0.000 description 3
• 230000036757 core body temperature Effects 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• 230000003247 decreasing effect Effects 0.000 description 3
• 239000008121 dextrose Substances 0.000 description 3
• 238000002405 diagnostic procedure Methods 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• 238000009826 distribution Methods 0.000 description 3
• 238000001647 drug administration Methods 0.000 description 3
• 239000000975 dye Substances 0.000 description 3
• 239000003995 emulsifying agent Substances 0.000 description 3
• 206010014599 encephalitis Diseases 0.000 description 3
• 238000005516 engineering process Methods 0.000 description 3
• 239000003623 enhancer Substances 0.000 description 3
• KGPPDNUWZNWPSI-UHFFFAOYSA-N flurotyl Chemical group FC(F)(F)COCC(F)(F)F KGPPDNUWZNWPSI-UHFFFAOYSA-N 0.000 description 3
• 235000019264 food flavour enhancer Nutrition 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 210000003128 head Anatomy 0.000 description 3
• 230000036541 health Effects 0.000 description 3
• 210000001320 hippocampus Anatomy 0.000 description 3
• 208000034287 idiopathic generalized susceptibility to 7 epilepsy Diseases 0.000 description 3
• 208000014674 injury Diseases 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 239000007951 isotonicity adjuster Substances 0.000 description 3
• 229960001848 lamotrigine Drugs 0.000 description 3
• PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 3
• 210000003141 lower extremity Anatomy 0.000 description 3
• 201000006417 multiple sclerosis Diseases 0.000 description 3
• 230000035772 mutation Effects 0.000 description 3
• 208000022145 neurocutaneous syndrome Diseases 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 235000019198 oils Nutrition 0.000 description 3
• 208000013667 paroxysmal dyskinesia Diseases 0.000 description 3
• 201000003040 photosensitive epilepsy Diseases 0.000 description 3
• 239000004033 plastic Substances 0.000 description 3
• 229920003023 plastic Polymers 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000002335 preservative effect Effects 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 230000001737 promoting effect Effects 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 239000000018 receptor agonist Substances 0.000 description 3
• 229940044601 receptor agonist Drugs 0.000 description 3
• 229940076279 serotonin Drugs 0.000 description 3
• 239000003244 serotonin 2B agonist Substances 0.000 description 3
• 239000013589 supplement Substances 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• 206010042772 syncope Diseases 0.000 description 3
• 208000011580 syndromic disease Diseases 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 201000008914 temporal lobe epilepsy Diseases 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 3
• 239000000080 wetting agent Substances 0.000 description 3
• AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 2
• VLPIATFUUWWMKC-SNVBAGLBSA-N (2r)-1-(2,6-dimethylphenoxy)propan-2-amine Chemical compound C[C@@H](N)COC1=C(C)C=CC=C1C VLPIATFUUWWMKC-SNVBAGLBSA-N 0.000 description 2
• BVJDPWSJTZGLTJ-ZIAGYGMSSA-N (2r)-n-[(1r)-1-phenylethyl]-1-[3-(trifluoromethyl)phenyl]propan-2-amine Chemical compound C([C@@H](C)N[C@H](C)C=1C=CC=CC=1)C1=CC=CC(C(F)(F)F)=C1 BVJDPWSJTZGLTJ-ZIAGYGMSSA-N 0.000 description 2
• RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 2
• WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 2
• 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 2
• ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 2
• JPHQCDCEBDRIOL-UHFFFAOYSA-N 1-[3-(trifluoromethyl)phenyl]propan-2-one Chemical compound CC(=O)CC1=CC=CC(C(F)(F)F)=C1 JPHQCDCEBDRIOL-UHFFFAOYSA-N 0.000 description 2
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 2
• 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 2
• USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 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
• 241000283690 Bos taurus Species 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• 102000018208 Cannabinoid Receptor Human genes 0.000 description 2
• 108050007331 Cannabinoid receptor Proteins 0.000 description 2
• 241000283707 Capra Species 0.000 description 2
• 201000001913 Childhood absence epilepsy Diseases 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 241000557626 Corvus corax Species 0.000 description 2
• 206010059866 Drug resistance Diseases 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 241000283086 Equidae Species 0.000 description 2
• 206010016173 Fall Diseases 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
• 101000625846 Homo sapiens TBC domain-containing protein kinase-like protein Proteins 0.000 description 2
• 206010021118 Hypotonia Diseases 0.000 description 2
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
• 201000006347 Intellectual Disability Diseases 0.000 description 2
• 239000004166 Lanolin Substances 0.000 description 2
• NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 2
• 208000007379 Muscle Hypotonia Diseases 0.000 description 2
• CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 2
• 208000025966 Neurological disease Diseases 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 2
• 241001494479 Pecora Species 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 206010037660 Pyrexia Diseases 0.000 description 2
• 108010052164 Sodium Channels Proteins 0.000 description 2
• 102000018674 Sodium Channels Human genes 0.000 description 2
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
• 238000000692 Student's t-test Methods 0.000 description 2
• 208000023944 Sudden Unexpected Death in Epilepsy Diseases 0.000 description 2
• 241000282887 Suidae Species 0.000 description 2
• 102100024750 TBC domain-containing protein kinase-like protein Human genes 0.000 description 2
• MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
• 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 description 2
• 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 description 2
• 208000028311 absence seizure Diseases 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 230000036982 action potential Effects 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 2
• 210000004727 amygdala Anatomy 0.000 description 2
• 239000000730 antalgic agent Substances 0.000 description 2
• 239000000935 antidepressant agent Substances 0.000 description 2
• 229940005513 antidepressants Drugs 0.000 description 2
• ATALOFNDEOCMKK-OITMNORJSA-N aprepitant Chemical compound O([C@@H]([C@@H]1C=2C=CC(F)=CC=2)O[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CCN1CC1=NNC(=O)N1 ATALOFNDEOCMKK-OITMNORJSA-N 0.000 description 2
• 208000008233 autosomal dominant nocturnal frontal lobe epilepsy Diseases 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 238000004166 bioassay Methods 0.000 description 2
• 230000002051 biphasic effect Effects 0.000 description 2
• 230000008499 blood brain barrier function Effects 0.000 description 2
• 210000001218 blood-brain barrier Anatomy 0.000 description 2
• ZRIHAIZYIMGOAB-UHFFFAOYSA-N butabarbital Chemical compound CCC(C)C1(CC)C(=O)NC(=O)NC1=O ZRIHAIZYIMGOAB-UHFFFAOYSA-N 0.000 description 2
• YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 229960000590 celecoxib Drugs 0.000 description 2
• RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 239000012069 chiral reagent Substances 0.000 description 2
• 229960004606 clomipramine Drugs 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
• OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 239000008367 deionised water Substances 0.000 description 2
• 229910021641 deionized water Inorganic materials 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• 238000003745 diagnosis Methods 0.000 description 2
• XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 description 2
• ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
• 229960002866 duloxetine Drugs 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 210000003414 extremity Anatomy 0.000 description 2
• 230000001815 facial effect Effects 0.000 description 2
• 229960001419 fenoprofen Drugs 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 229960002464 fluoxetine Drugs 0.000 description 2
• 229950000929 flurotyl Drugs 0.000 description 2
• 235000013305 food Nutrition 0.000 description 2
• 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 230000009395 genetic defect Effects 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• 235000011187 glycerol Nutrition 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 239000012456 homogeneous solution Substances 0.000 description 2
• OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
• 229960001680 ibuprofen Drugs 0.000 description 2
• 229960004801 imipramine Drugs 0.000 description 2
• BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 238000007913 intrathecal administration Methods 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 2
• 229960000991 ketoprofen Drugs 0.000 description 2
• 229940039717 lanolin Drugs 0.000 description 2
• 235000019388 lanolin Nutrition 0.000 description 2
• 229960004194 lidocaine Drugs 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 230000033001 locomotion Effects 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 230000010534 mechanism of action Effects 0.000 description 2
• 230000002503 metabolic effect Effects 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
• 229960003404 mexiletine Drugs 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
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
• 229960002009 naproxen Drugs 0.000 description 2
• CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 2
• 230000001537 neural effect Effects 0.000 description 2
• 210000002569 neuron Anatomy 0.000 description 2
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
• 238000007474 nonparametric Mann- Whitney U test Methods 0.000 description 2
• 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 230000003204 osmotic effect Effects 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 238000004806 packaging method and process Methods 0.000 description 2
• 229940124641 pain reliever Drugs 0.000 description 2
• 229960005489 paracetamol Drugs 0.000 description 2
• 229960002296 paroxetine Drugs 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 239000002504 physiological saline solution Substances 0.000 description 2
• 229940068917 polyethylene glycols Drugs 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 2
• 238000012877 positron emission topography Methods 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 230000000750 progressive effect Effects 0.000 description 2
• 239000002287 radioligand Substances 0.000 description 2
• 238000011552 rat model Methods 0.000 description 2
• 229940044551 receptor antagonist Drugs 0.000 description 2
• 239000002464 receptor antagonist Substances 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 2
• 239000008247 solid mixture Substances 0.000 description 2
• 238000007619 statistical method Methods 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 231100000331 toxic Toxicity 0.000 description 2
• 230000002588 toxic effect Effects 0.000 description 2
• 230000001960 triggered effect Effects 0.000 description 2
• 210000001364 upper extremity Anatomy 0.000 description 2
• 229940102566 valproate Drugs 0.000 description 2
• 229960004688 venlafaxine Drugs 0.000 description 2
• RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
• GJJFMKBJSRMPLA-HIFRSBDPSA-N (1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenyl-1-cyclopropanecarboxamide Chemical compound C=1C=CC=CC=1[C@@]1(C(=O)N(CC)CC)C[C@@H]1CN GJJFMKBJSRMPLA-HIFRSBDPSA-N 0.000 description 1
• RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
• PTJADDMMFYXMMG-LJQANCHMSA-N (1r)-1-(4-fluorophenyl)-1-[3-(methylamino)propyl]-3h-2-benzofuran-5-carbonitrile Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCNC)=CC=C(F)C=C1 PTJADDMMFYXMMG-LJQANCHMSA-N 0.000 description 1
• CBQGYUDMJHNJBX-OALUTQOASA-N (2S)-2-[(S)-(2-ethoxyphenoxy)-phenylmethyl]morpholine Chemical compound CCOC1=CC=CC=C1O[C@@H](C=1C=CC=CC=1)[C@H]1OCCNC1 CBQGYUDMJHNJBX-OALUTQOASA-N 0.000 description 1
• YWPHCCPCQOJSGZ-LLVKDONJSA-N (2r)-2-[(2-ethoxyphenoxy)methyl]morpholine Chemical compound CCOC1=CC=CC=C1OC[C@@H]1OCCNC1 YWPHCCPCQOJSGZ-LLVKDONJSA-N 0.000 description 1
• ONQMRZCDUGMKAW-DTPOWOMPSA-N (2r)-n-[(1r)-1-phenylethyl]-1-[3-(trifluoromethyl)phenyl]propan-2-amine;hydrochloride Chemical compound Cl.C([C@@H](C)N[C@H](C)C=1C=CC=CC=1)C1=CC=CC(C(F)(F)F)=C1 ONQMRZCDUGMKAW-DTPOWOMPSA-N 0.000 description 1
• CCIWVEMVBWEMCY-RCFOMQFPSA-N (2s)-1-[(3as,4s,7as)-4-hydroxy-4-(2-methoxyphenyl)-7,7-diphenyl-1,3,3a,5,6,7a-hexahydroisoindol-2-yl]-2-(2-methoxyphenyl)propan-1-one Chemical compound COC1=CC=CC=C1[C@H](C)C(=O)N1C[C@H](C(CC[C@@]2(O)C=3C(=CC=CC=3)OC)(C=3C=CC=CC=3)C=3C=CC=CC=3)[C@H]2C1 CCIWVEMVBWEMCY-RCFOMQFPSA-N 0.000 description 1
• FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 description 1
• LDXQLWNPGRANTO-GOSISDBHSA-N (9r)-7-[[3,5-bis(trifluoromethyl)phenyl]methyl]-9-methyl-5-(4-methylphenyl)-8,9,10,11-tetrahydro-[1,4]diazocino[2,1-g][1,7]naphthyridine-6,13-dione Chemical compound C([C@H](CN(CC=1C=C(C=C(C=1)C(F)(F)F)C(F)(F)F)C1=O)C)CN(C(C2=NC=CC=C22)=O)C1=C2C1=CC=C(C)C=C1 LDXQLWNPGRANTO-GOSISDBHSA-N 0.000 description 1
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
• LZTSCEYDCZBRCJ-UHFFFAOYSA-N 1,2-dihydro-1,2,4-triazol-3-one Chemical compound OC=1N=CNN=1 LZTSCEYDCZBRCJ-UHFFFAOYSA-N 0.000 description 1
• 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 1
• BFUUJUGQJUTPAF-UHFFFAOYSA-N 2-(3-amino-4-propoxybenzoyl)oxyethyl-diethylazanium;chloride Chemical compound [Cl-].CCCOC1=CC=C(C(=O)OCC[NH+](CC)CC)C=C1N BFUUJUGQJUTPAF-UHFFFAOYSA-N 0.000 description 1
• HJOCKFVCMLCPTP-UHFFFAOYSA-N 2-[(2-ethoxyphenoxy)methyl]morpholine;hydron;chloride Chemical compound Cl.CCOC1=CC=CC=C1OCC1OCCNC1 HJOCKFVCMLCPTP-UHFFFAOYSA-N 0.000 description 1
• KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 description 1
• YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 description 1
• XKSAJZSJKURQRX-UHFFFAOYSA-N 2-acetyloxy-5-(4-fluorophenyl)benzoic acid Chemical compound C1=C(C(O)=O)C(OC(=O)C)=CC=C1C1=CC=C(F)C=C1 XKSAJZSJKURQRX-UHFFFAOYSA-N 0.000 description 1
• GNXFOGHNGIVQEH-UHFFFAOYSA-N 2-hydroxy-3-(2-methoxyphenoxy)propyl carbamate Chemical compound COC1=CC=CC=C1OCC(O)COC(N)=O GNXFOGHNGIVQEH-UHFFFAOYSA-N 0.000 description 1
• VPIXQGUBUKFLRF-UHFFFAOYSA-N 3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N-methyl-1-propanamine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCNC)C2=CC=CC=C21 VPIXQGUBUKFLRF-UHFFFAOYSA-N 0.000 description 1
• FWYRGHMKHZXXQX-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-2-(dimethylamino)-2-methylpropan-1-ol Chemical compound CN(C)C(C)(CO)CC1=CC=C(Cl)C(Cl)=C1 FWYRGHMKHZXXQX-UHFFFAOYSA-N 0.000 description 1
• WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 description 1
• 102000056834 5-HT2 Serotonin Receptors Human genes 0.000 description 1
• 108091005479 5-HT2 receptors Proteins 0.000 description 1
• LPVNIMONLMBGBU-SFHVURJKSA-N 5-[[(3S)-1-benzylpyrrolidin-3-yl]-methylamino]-6-methyl-N-(1,3-thiazol-4-yl)pyridine-2-sulfonamide Chemical compound C(C1=CC=CC=C1)N1C[C@H](CC1)N(C=1C=CC(=NC=1C)S(=O)(=O)NC=1N=CSC=1)C LPVNIMONLMBGBU-SFHVURJKSA-N 0.000 description 1
• 102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 description 1
• 101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 description 1
• 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
• 229920000936 Agarose Polymers 0.000 description 1
• 101710195183 Alpha-bungarotoxin Proteins 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 1
• 102100021257 Beta-secretase 1 Human genes 0.000 description 1
• OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 241001466804 Carnivora Species 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 108091006146 Channels Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 208000017667 Chronic Disease Diseases 0.000 description 1
• GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
• 208000033001 Complex partial seizures Diseases 0.000 description 1
• 208000034656 Contusions Diseases 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 239000004375 Dextrin Substances 0.000 description 1
• 229920001353 Dextrin Polymers 0.000 description 1
• 102000009025 Endorphins Human genes 0.000 description 1
• 108010049140 Endorphins Proteins 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• 208000001914 Fragile X syndrome Diseases 0.000 description 1
• 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• JMBQKKAJIKAWKF-UHFFFAOYSA-N Glutethimide Chemical compound C=1C=CC=CC=1C1(CC)CCC(=O)NC1=O JMBQKKAJIKAWKF-UHFFFAOYSA-N 0.000 description 1
• 101150104779 HTR2A gene Proteins 0.000 description 1
• 244000020551 Helianthus annuus Species 0.000 description 1
• 235000003222 Helianthus annuus Nutrition 0.000 description 1
• GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
• 241001272567 Hominoidea Species 0.000 description 1
• 101000684826 Homo sapiens Sodium channel protein type 2 subunit alpha Proteins 0.000 description 1
• 101000654381 Homo sapiens Sodium channel protein type 8 subunit alpha Proteins 0.000 description 1
• 101000890887 Homo sapiens Trace amine-associated receptor 1 Proteins 0.000 description 1
• 101150013372 Htr2c gene Proteins 0.000 description 1
• AKOAEVOSDHIVFX-UHFFFAOYSA-N Hydroxybupropion Chemical compound OCC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 AKOAEVOSDHIVFX-UHFFFAOYSA-N 0.000 description 1
• 206010020880 Hypertrophy Diseases 0.000 description 1
• 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 1
• UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
• 102000005453 KCNQ2 Potassium Channel Human genes 0.000 description 1
• 108010006746 KCNQ2 Potassium Channel 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
• 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 1
• 208000005870 Lafora disease Diseases 0.000 description 1
• OZYUPQUCAUTOBP-QXAKKESOSA-N Levallorphan Chemical compound C([C@H]12)CCC[C@@]11CCN(CC=C)[C@@H]2CC2=CC=C(O)C=C21 OZYUPQUCAUTOBP-QXAKKESOSA-N 0.000 description 1
• JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 description 1
• 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
• 238000000585 Mann–Whitney U test Methods 0.000 description 1
• SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 1
• ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 1
• 244000246386 Mentha pulegium Species 0.000 description 1
• 235000016257 Mentha pulegium Nutrition 0.000 description 1
• 235000004357 Mentha x piperita Nutrition 0.000 description 1
• NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical compound NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 1
• JEYCTXHKTXCGPB-UHFFFAOYSA-N Methaqualone Chemical compound CC1=CC=CC=C1N1C(=O)C2=CC=CC=C2N=C1C JEYCTXHKTXCGPB-UHFFFAOYSA-N 0.000 description 1
• NZXKDOXHBHYTKP-UHFFFAOYSA-N Metohexital Chemical compound CCC#CC(C)C1(CC=C)C(=O)NC(=O)N(C)C1=O NZXKDOXHBHYTKP-UHFFFAOYSA-N 0.000 description 1
• UEQUQVLFIPOEMF-UHFFFAOYSA-N Mianserin Chemical compound C1C2=CC=CC=C2N2CCN(C)CC2C2=CC=CC=C21 UEQUQVLFIPOEMF-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
• 208000037004 Myoclonic-astatic epilepsy Diseases 0.000 description 1
• 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 1
• BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 1
• WJBLNOPPDWQMCH-MBPVOVBZSA-N Nalmefene Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=C)O)CC1)O)CC1CC1 WJBLNOPPDWQMCH-MBPVOVBZSA-N 0.000 description 1
• UIQMVEYFGZJHCZ-SSTWWWIQSA-N Nalorphine Chemical compound C([C@@H](N(CC1)CC=C)[C@@H]2C=C[C@@H]3O)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 UIQMVEYFGZJHCZ-SSTWWWIQSA-N 0.000 description 1
• 206010029350 Neurotoxicity Diseases 0.000 description 1
• PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 1
• KYYIDSXMWOZKMP-UHFFFAOYSA-N O-desmethylvenlafaxine Chemical compound C1CCCCC1(O)C(CN(C)C)C1=CC=C(O)C=C1 KYYIDSXMWOZKMP-UHFFFAOYSA-N 0.000 description 1
• BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
• UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 206010033799 Paralysis Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• 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 description 1
• 206010034972 Photosensitivity reaction Diseases 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• QPCVHQBVMYCJOM-UHFFFAOYSA-N Propiverine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OCCC)C(=O)OC1CCN(C)CC1 QPCVHQBVMYCJOM-UHFFFAOYSA-N 0.000 description 1
• 206010038669 Respiratory arrest Diseases 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 101100420804 Schizosaccharomyces pombe (strain 972 / ATCC 24843) scn1 gene Proteins 0.000 description 1
• 241001486234 Sciota Species 0.000 description 1
• 102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 description 1
• 108010012996 Serotonin Plasma Membrane Transport Proteins Proteins 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• 102100023150 Sodium channel protein type 2 subunit alpha Human genes 0.000 description 1
• 102100031371 Sodium channel protein type 8 subunit alpha Human genes 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 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 1
• 102000003141 Tachykinin Human genes 0.000 description 1
• DRHKJLXJIQTDTD-OAHLLOKOSA-N Tamsulosine Chemical compound CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-OAHLLOKOSA-N 0.000 description 1
• PPWHTZKZQNXVAE-UHFFFAOYSA-N Tetracaine hydrochloride Chemical compound Cl.CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 PPWHTZKZQNXVAE-UHFFFAOYSA-N 0.000 description 1
• IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 description 1
• 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 description 1
• 206010044221 Toxic encephalopathy Diseases 0.000 description 1
• 102100040114 Trace amine-associated receptor 1 Human genes 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
• 208000003443 Unconsciousness Diseases 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• DMEPDNFRHUGNPT-UHFFFAOYSA-N [5-(diethylamino)-2-methylpent-3-yn-2-yl] 2-cyclohexyl-2-hydroxy-2-phenylacetate Chemical compound C=1C=CC=CC=1C(O)(C(=O)OC(C)(C)C#CCN(CC)CC)C1CCCCC1 DMEPDNFRHUGNPT-UHFFFAOYSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
• 229960004373 acetylcholine Drugs 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 239000000464 adrenergic agent Substances 0.000 description 1
• 239000003570 air Substances 0.000 description 1
• 229940087458 alcaine Drugs 0.000 description 1
• 125000003158 alcohol group Chemical group 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 1
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• 208000011916 alternating hemiplegia Diseases 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 239000012080 ambient air Substances 0.000 description 1
• 150000001414 amino alcohols Chemical class 0.000 description 1
• 229960000836 amitriptyline Drugs 0.000 description 1
• KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
• 229960001301 amobarbital Drugs 0.000 description 1
• 229940025084 amphetamine Drugs 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 229940035676 analgesics Drugs 0.000 description 1
• 230000003288 anthiarrhythmic effect Effects 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000003579 anti-obesity Effects 0.000 description 1
• 230000000573 anti-seizure effect Effects 0.000 description 1
• 239000003416 antiarrhythmic agent Substances 0.000 description 1
• 229940125681 anticonvulsant agent Drugs 0.000 description 1
• 239000003472 antidiabetic agent Substances 0.000 description 1
• 229940125708 antidiabetic agent Drugs 0.000 description 1
• 229940125715 antihistaminic agent Drugs 0.000 description 1
• 239000000739 antihistaminic agent Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 239000002249 anxiolytic agent Substances 0.000 description 1
• 230000000949 anxiolytic effect Effects 0.000 description 1
• 229940005530 anxiolytics Drugs 0.000 description 1
• 239000002830 appetite depressant Substances 0.000 description 1
• 229960001372 aprepitant Drugs 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 101150080892 asp2 gene Proteins 0.000 description 1
• 238000013096 assay test Methods 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 229960002430 atomoxetine Drugs 0.000 description 1
• 229960000794 baclofen Drugs 0.000 description 1
• 229940125717 barbiturate Drugs 0.000 description 1
• 239000012724 barbiturate sedative Substances 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 229940092738 beeswax Drugs 0.000 description 1
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 239000012496 blank sample Substances 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
• 230000036760 body temperature Effects 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical class CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 1
• 229940015694 butabarbital Drugs 0.000 description 1
• SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical class NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 description 1
• 229960002504 capsaicin Drugs 0.000 description 1
• 235000017663 capsaicin Nutrition 0.000 description 1
• DRCMAZOSEIMCHM-UHFFFAOYSA-N capsazepine Chemical compound C1C=2C=C(O)C(O)=CC=2CCCN1C(=S)NCCC1=CC=C(Cl)C=C1 DRCMAZOSEIMCHM-UHFFFAOYSA-N 0.000 description 1
• 229960000623 carbamazepine Drugs 0.000 description 1
• FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 230000009787 cardiac fibrosis Effects 0.000 description 1
• 229960004587 carisoprodol Drugs 0.000 description 1
• OFZCIYFFPZCNJE-UHFFFAOYSA-N carisoprodol Chemical compound NC(=O)OCC(C)(CCC)COC(=O)NC(C)C OFZCIYFFPZCNJE-UHFFFAOYSA-N 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 229950000303 cericlamine Drugs 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 229940112822 chewing gum Drugs 0.000 description 1
• 235000015218 chewing gum Nutrition 0.000 description 1
• 239000002727 chloride channel blocking agent Substances 0.000 description 1
• 229960003633 chlorzoxazone Drugs 0.000 description 1
• TZFWDZFKRBELIQ-UHFFFAOYSA-N chlorzoxazone Chemical compound ClC1=CC=C2OC(O)=NC2=C1 TZFWDZFKRBELIQ-UHFFFAOYSA-N 0.000 description 1
• 230000001713 cholinergic effect Effects 0.000 description 1
• 239000000544 cholinesterase inhibitor Substances 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 230000002060 circadian Effects 0.000 description 1
• 229960001653 citalopram Drugs 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 229960002896 clonidine Drugs 0.000 description 1
• 239000011280 coal tar Substances 0.000 description 1
• 229960003920 cocaine Drugs 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 229960004126 codeine Drugs 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 208000013500 continuous spikes and waves during sleep Diseases 0.000 description 1
• 239000003179 convulsant agent Substances 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 210000004087 cornea Anatomy 0.000 description 1
• 210000003618 cortical neuron Anatomy 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229940111134 coxibs Drugs 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• FSIRGTNPQFDCCD-QGMBQPNBSA-N cyanodothiepin Chemical compound C1SC2=CC=C(C#N)C=C2C(=C/CCN(C)C)/C2=CC=CC=C21 FSIRGTNPQFDCCD-QGMBQPNBSA-N 0.000 description 1
• 229960003572 cyclobenzaprine Drugs 0.000 description 1
• JURKNVYFZMSNLP-UHFFFAOYSA-N cyclobenzaprine Chemical compound C1=CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 JURKNVYFZMSNLP-UHFFFAOYSA-N 0.000 description 1
• 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
• 229950007605 dapitant Drugs 0.000 description 1
• USRHYDPUVLEVMC-FQEVSTJZSA-N dapoxetine Chemical compound C1([C@H](CCOC=2C3=CC=CC=C3C=CC=2)N(C)C)=CC=CC=C1 USRHYDPUVLEVMC-FQEVSTJZSA-N 0.000 description 1
• 229960005217 dapoxetine Drugs 0.000 description 1
• HXGBXQDTNZMWGS-RUZDIDTESA-N darifenacin Chemical compound C=1C=CC=CC=1C([C@H]1CN(CCC=2C=C3CCOC3=CC=2)CC1)(C(=O)N)C1=CC=CC=C1 HXGBXQDTNZMWGS-RUZDIDTESA-N 0.000 description 1
• 229960002677 darifenacin Drugs 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 229960003314 deracoxib Drugs 0.000 description 1
• WAZQAZKAZLXFMK-UHFFFAOYSA-N deracoxib Chemical compound C1=C(F)C(OC)=CC=C1C1=CC(C(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 WAZQAZKAZLXFMK-UHFFFAOYSA-N 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• SRPXSILJHWNFMK-ZBEGNZNMSA-N desmethylsertraline Chemical class C1([C@@H]2CC[C@@H](C3=CC=CC=C32)N)=CC=C(Cl)C(Cl)=C1 SRPXSILJHWNFMK-ZBEGNZNMSA-N 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 229960003957 dexamethasone Drugs 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 235000019425 dextrin Nutrition 0.000 description 1
• 229960004193 dextropropoxyphene Drugs 0.000 description 1
• XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 description 1
• NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• 229960002069 diamorphine Drugs 0.000 description 1
• ATKXDQOHNICLQW-UHFFFAOYSA-N dichloralphenazone Chemical compound OC(O)C(Cl)(Cl)Cl.OC(O)C(Cl)(Cl)Cl.CN1C(C)=CC(=O)N1C1=CC=CC=C1 ATKXDQOHNICLQW-UHFFFAOYSA-N 0.000 description 1
• 229960005422 dichloralphenazone Drugs 0.000 description 1
• 229960001259 diclofenac Drugs 0.000 description 1
• DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 229960000616 diflunisal Drugs 0.000 description 1
• HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
• RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 1
• 229960000920 dihydrocodeine Drugs 0.000 description 1
• XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
• 229960002986 dinoprostone Drugs 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• 229960003530 donepezil Drugs 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 230000005584 early death Effects 0.000 description 1
• 201000009028 early myoclonic encephalopathy Diseases 0.000 description 1
• 238000002635 electroconvulsive therapy Methods 0.000 description 1
• 238000002001 electrophysiology Methods 0.000 description 1
• 230000007831 electrophysiology Effects 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 210000001353 entorhinal cortex Anatomy 0.000 description 1
• 201000002933 epilepsy with generalized tonic-clonic seizures Diseases 0.000 description 1
• 230000001787 epileptiform Effects 0.000 description 1
• 229960004341 escitalopram Drugs 0.000 description 1
• WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 229960005293 etodolac Drugs 0.000 description 1
• XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
• 229960004945 etoricoxib Drugs 0.000 description 1
• MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• OJSFTALXCYKKFQ-YLJYHZDGSA-N femoxetine Chemical compound C1=CC(OC)=CC=C1OC[C@@H]1[C@@H](C=2C=CC=CC=2)CCN(C)C1 OJSFTALXCYKKFQ-YLJYHZDGSA-N 0.000 description 1
• 229950003930 femoxetine Drugs 0.000 description 1
• 229960001395 fenbufen Drugs 0.000 description 1
• ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 description 1
• 229960002428 fentanyl Drugs 0.000 description 1
• PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 1
• 229950000761 fezolamine Drugs 0.000 description 1
• NELSQLPTEWCHQW-UHFFFAOYSA-N fezolamine Chemical compound N=1N(CCCN(C)C)C=C(C=2C=CC=CC=2)C=1C1=CC=CC=C1 NELSQLPTEWCHQW-UHFFFAOYSA-N 0.000 description 1
• 238000010304 firing Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 229950007979 flufenisal Drugs 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 229960002390 flurbiprofen Drugs 0.000 description 1
• SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
• 229960004038 fluvoxamine Drugs 0.000 description 1
• CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 210000002683 foot Anatomy 0.000 description 1
• 210000004744 fore-foot Anatomy 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 229960002870 gabapentin Drugs 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 229960002972 glutethimide Drugs 0.000 description 1
• 210000005003 heart tissue Anatomy 0.000 description 1
• 210000003709 heart valve Anatomy 0.000 description 1
• 238000000265 homogenisation Methods 0.000 description 1
• 235000001050 hortel pimenta Nutrition 0.000 description 1
• LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 description 1
• 229960000240 hydrocodone Drugs 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 description 1
• 229960001410 hydromorphone Drugs 0.000 description 1
• 229950006314 ifoxetine Drugs 0.000 description 1
• ZHFIAFNZGWCLHU-YPMHNXCESA-N ifoxetine Chemical compound CC1=CC=CC(O[C@@H]2[C@@H](CNCC2)O)=C1C ZHFIAFNZGWCLHU-YPMHNXCESA-N 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000010874 in vitro model Methods 0.000 description 1
• 210000004283 incisor Anatomy 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 229960000905 indomethacin Drugs 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 210000001153 interneuron Anatomy 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
• 229960001888 ipratropium Drugs 0.000 description 1
• 210000001847 jaw Anatomy 0.000 description 1
• 230000000366 juvenile effect Effects 0.000 description 1
• VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 1
• 229950006874 kainic acid Drugs 0.000 description 1
• 229960004752 ketorolac Drugs 0.000 description 1
• OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229950005286 lanepitant Drugs 0.000 description 1
• 230000002045 lasting effect Effects 0.000 description 1
• 231100000225 lethality Toxicity 0.000 description 1
• VNYSSYRCGWBHLG-AMOLWHMGSA-M leukotriene B4(1-) Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC([O-])=O VNYSSYRCGWBHLG-AMOLWHMGSA-M 0.000 description 1
• 229960000263 levallorphan Drugs 0.000 description 1
• 229960004002 levetiracetam Drugs 0.000 description 1
• HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 description 1
• 229960003406 levorphanol Drugs 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
• MJJDYOLPMGIWND-UHFFFAOYSA-N litoxetine Chemical compound C=1C=C2C=CC=CC2=CC=1COC1CCNCC1 MJJDYOLPMGIWND-UHFFFAOYSA-N 0.000 description 1
• 229950004138 litoxetine Drugs 0.000 description 1
• 239000003589 local anesthetic agent Substances 0.000 description 1
• 229960005015 local anesthetics Drugs 0.000 description 1
• 229960002813 lofepramine Drugs 0.000 description 1
• SAPNXPWPAUFAJU-UHFFFAOYSA-N lofepramine Chemical compound C12=CC=CC=C2CCC2=CC=CC=C2N1CCCN(C)CC(=O)C1=CC=C(Cl)C=C1 SAPNXPWPAUFAJU-UHFFFAOYSA-N 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 229960000994 lumiracoxib Drugs 0.000 description 1
• KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 229960004090 maprotiline Drugs 0.000 description 1
• QSLMDECMDJKHMQ-GSXCWMCISA-N maprotiline Chemical compound C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 229960003803 meclofenamic acid Drugs 0.000 description 1
• 238000013160 medical therapy Methods 0.000 description 1
• 229960003464 mefenamic acid Drugs 0.000 description 1
• 229960001929 meloxicam Drugs 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000036630 mental development Effects 0.000 description 1
• ALARQZQTBTVLJV-UHFFFAOYSA-N mephobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)N(C)C1=O ALARQZQTBTVLJV-UHFFFAOYSA-N 0.000 description 1
• 229960004815 meprobamate Drugs 0.000 description 1
• 229960001797 methadone Drugs 0.000 description 1
• 229960002803 methaqualone Drugs 0.000 description 1
• 229960002330 methocarbamol Drugs 0.000 description 1
• 229960002683 methohexital Drugs 0.000 description 1
• STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
• 229940012189 methyl orange Drugs 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 229960001047 methyl salicylate Drugs 0.000 description 1
• CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
• XLTANAWLDBYGFU-UHFFFAOYSA-N methyllycaconitine hydrochloride Natural products C1CC(OC)C2(C3C4OC)C5CC(C(C6)OC)C(OC)C5C6(O)C4(O)C2N(CC)CC31COC(=O)C1=CC=CC=C1N1C(=O)CC(C)C1=O XLTANAWLDBYGFU-UHFFFAOYSA-N 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 229960001703 methylphenobarbital Drugs 0.000 description 1
• 229960000907 methylthioninium chloride Drugs 0.000 description 1
• 229960003955 mianserin Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 239000004005 microsphere Substances 0.000 description 1
• 229960000600 milnacipran Drugs 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 229940042472 mineral oil Drugs 0.000 description 1
• 229960001165 modafinil Drugs 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 229960005181 morphine Drugs 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• 239000000472 muscarinic agonist Substances 0.000 description 1
• 239000003149 muscarinic antagonist Substances 0.000 description 1
• 230000003551 muscarinic effect Effects 0.000 description 1
• 230000004118 muscle contraction Effects 0.000 description 1
• 229940035363 muscle relaxants Drugs 0.000 description 1
• 230000002151 myoclonic effect Effects 0.000 description 1
• 208000016313 myoclonic-astastic epilepsy Diseases 0.000 description 1
• 239000003158 myorelaxant agent Substances 0.000 description 1
• CVXJAPZTZWLRBP-MUUNZHRXSA-N n-[(2r)-1-[acetyl-[(2-methoxyphenyl)methyl]amino]-3-(1h-indol-3-yl)propan-2-yl]-2-(4-piperidin-1-ylpiperidin-1-yl)acetamide Chemical compound COC1=CC=CC=C1CN(C(C)=O)C[C@H](NC(=O)CN1CCC(CC1)N1CCCCC1)CC1=CNC2=CC=CC=C12 CVXJAPZTZWLRBP-MUUNZHRXSA-N 0.000 description 1
• OLYXPBZBZBVRGD-UHFFFAOYSA-N n-[2-(4-amino-6,7-dimethoxy-5-pyridin-2-ylquinazolin-2-yl)-3,4-dihydro-1h-isoquinolin-5-yl]methanesulfonamide Chemical compound COC=1C(OC)=CC2=NC(N3CC4=C(C(=CC=C4)NS(C)(=O)=O)CC3)=NC(N)=C2C=1C1=CC=CC=N1 OLYXPBZBZBVRGD-UHFFFAOYSA-N 0.000 description 1
• NYRWESBUIKRJMS-UHFFFAOYSA-N n-[2-methoxy-5-(trifluoromethoxy)phenyl]-n-methyl-2-phenylpiperidin-3-amine Chemical compound COC1=CC=C(OC(F)(F)F)C=C1N(C)C1C(C=2C=CC=CC=2)NCCC1 NYRWESBUIKRJMS-UHFFFAOYSA-N 0.000 description 1
• 229960004270 nabumetone Drugs 0.000 description 1
• 229960005297 nalmefene Drugs 0.000 description 1
• 229960000938 nalorphine Drugs 0.000 description 1
• 229960004127 naloxone Drugs 0.000 description 1
• UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 1
• 229940097496 nasal spray Drugs 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 229960001800 nefazodone Drugs 0.000 description 1
• VRBKIVRKKCLPHA-UHFFFAOYSA-N nefazodone Chemical compound O=C1N(CCOC=2C=CC=CC=2)C(CC)=NN1CCCN(CC1)CCN1C1=CC=CC(Cl)=C1 VRBKIVRKKCLPHA-UHFFFAOYSA-N 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 230000001722 neurochemical effect Effects 0.000 description 1
• 239000002742 neurokinin 1 receptor antagonist Substances 0.000 description 1
• 239000002746 neurokinin 2 receptor antagonist Substances 0.000 description 1
• 239000002740 neurokinin 3 receptor antagonist Substances 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 230000008587 neuronal excitability Effects 0.000 description 1
• 230000007135 neurotoxicity Effects 0.000 description 1
• 231100000228 neurotoxicity Toxicity 0.000 description 1
• 229960000965 nimesulide Drugs 0.000 description 1
• HYWYRSMBCFDLJT-UHFFFAOYSA-N nimesulide Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1=CC=CC=C1 HYWYRSMBCFDLJT-UHFFFAOYSA-N 0.000 description 1
• DLWSRGHNJVLJAH-UHFFFAOYSA-N nitroflurbiprofen Chemical compound FC1=CC(C(C(=O)OCCCCO[N+]([O-])=O)C)=CC=C1C1=CC=CC=C1 DLWSRGHNJVLJAH-UHFFFAOYSA-N 0.000 description 1
• 229960001073 nomifensine Drugs 0.000 description 1
• XXPANQJNYNUNES-UHFFFAOYSA-N nomifensine Chemical compound C12=CC=CC(N)=C2CN(C)CC1C1=CC=CC=C1 XXPANQJNYNUNES-UHFFFAOYSA-N 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 229940121367 non-opioid analgesics Drugs 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 239000000346 nonvolatile oil Substances 0.000 description 1
• 229940126569 noradrenaline reuptake inhibitor Drugs 0.000 description 1
• WIQRCHMSJFFONW-UHFFFAOYSA-N norfluoxetine Chemical compound C=1C=CC=CC=1C(CCN)OC1=CC=C(C(F)(F)F)C=C1 WIQRCHMSJFFONW-UHFFFAOYSA-N 0.000 description 1
• 229960001158 nortriptyline Drugs 0.000 description 1
• 229960004110 olsalazine Drugs 0.000 description 1
• QQBDLJCYGRGAKP-FOCLMDBBSA-N olsalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=C(C(O)=CC=2)C(O)=O)=C1 QQBDLJCYGRGAKP-FOCLMDBBSA-N 0.000 description 1
• 229960005343 ondansetron Drugs 0.000 description 1
• 239000008203 oral pharmaceutical composition Substances 0.000 description 1
• 229940100688 oral solution Drugs 0.000 description 1
• 230000000399 orthopedic effect Effects 0.000 description 1
• FDXQKWSTUZCCTM-UHFFFAOYSA-N oxaprotiline Chemical compound C12=CC=CC=C2C2(CC(O)CNC)C3=CC=CC=C3C1CC2 FDXQKWSTUZCCTM-UHFFFAOYSA-N 0.000 description 1
• 229960002739 oxaprozin Drugs 0.000 description 1
• OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
• 229960001816 oxcarbazepine Drugs 0.000 description 1
• CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 description 1
• 229960002085 oxycodone Drugs 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229960005118 oxymorphone Drugs 0.000 description 1
• 210000003695 paranasal sinus Anatomy 0.000 description 1
• 229960004662 parecoxib Drugs 0.000 description 1
• TZRHLKRLEZJVIJ-UHFFFAOYSA-N parecoxib Chemical compound C1=CC(S(=O)(=O)NC(=O)CC)=CC=C1C1=C(C)ON=C1C1=CC=CC=C1 TZRHLKRLEZJVIJ-UHFFFAOYSA-N 0.000 description 1
• 230000001314 paroxysmal effect Effects 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 229960001412 pentobarbital Drugs 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 238000004634 pharmacological analysis method Methods 0.000 description 1
• 229960002695 phenobarbital Drugs 0.000 description 1
• DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
• 229960002895 phenylbutazone Drugs 0.000 description 1
• VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
• 229960002036 phenytoin Drugs 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000036211 photosensitivity Effects 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229960002702 piroxicam Drugs 0.000 description 1
• QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 230000000270 postfertilization Effects 0.000 description 1
• 230000001144 postural effect Effects 0.000 description 1
• 238000012910 preclinical development Methods 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 229960001233 pregabalin Drugs 0.000 description 1
• AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 1
• 230000002028 premature Effects 0.000 description 1
• 230000000216 proconvulsive effect Effects 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 201000001204 progressive myoclonus epilepsy Diseases 0.000 description 1
• 229960003510 propiverine Drugs 0.000 description 1
• 210000004129 prosencephalon Anatomy 0.000 description 1
• XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 230000006920 protein precipitation Effects 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 208000002815 pulmonary hypertension Diseases 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 229960003770 reboxetine Drugs 0.000 description 1
• CBQGYUDMJHNJBX-RTBURBONSA-N reboxetine Chemical compound CCOC1=CC=CC=C1O[C@H](C=1C=CC=CC=1)[C@@H]1OCCNC1 CBQGYUDMJHNJBX-RTBURBONSA-N 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 238000002694 regional anesthesia Methods 0.000 description 1
• 230000001373 regressive effect Effects 0.000 description 1
• DSDNAKHZNJAGHN-UHFFFAOYSA-N resinferatoxin Natural products C1=C(O)C(OC)=CC(CC(=O)OCC=2CC3(O)C(=O)C(C)=CC3C34C(C)CC5(OC(O4)(CC=4C=CC=CC=4)OC5C3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-UHFFFAOYSA-N 0.000 description 1
• DSDNAKHZNJAGHN-MXTYGGKSSA-N resiniferatoxin Chemical compound C1=C(O)C(OC)=CC(CC(=O)OCC=2C[C@]3(O)C(=O)C(C)=C[C@H]3[C@@]34[C@H](C)C[C@@]5(O[C@@](O4)(CC=4C=CC=CC=4)O[C@@H]5[C@@H]3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-MXTYGGKSSA-N 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 230000004043 responsiveness Effects 0.000 description 1
• 230000000630 rising effect Effects 0.000 description 1
• 229960000371 rofecoxib Drugs 0.000 description 1
• RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 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
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 150000003902 salicylic acid esters Chemical class 0.000 description 1
• 229960002060 secobarbital Drugs 0.000 description 1
• KQPKPCNLIDLUMF-UHFFFAOYSA-N secobarbital Chemical compound CCCC(C)C1(CC=C)C(=O)NC(=O)NC1=O KQPKPCNLIDLUMF-UHFFFAOYSA-N 0.000 description 1
• 229940125723 sedative agent Drugs 0.000 description 1
• 239000000932 sedative agent Substances 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000000862 serotonergic effect Effects 0.000 description 1
• 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
• 239000000952 serotonin receptor agonist Substances 0.000 description 1
• 230000013275 serotonin uptake Effects 0.000 description 1
• 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
• 229960002073 sertraline Drugs 0.000 description 1
• VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 230000008054 signal transmission Effects 0.000 description 1
• 210000002460 smooth muscle Anatomy 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• 239000003195 sodium channel blocking agent Substances 0.000 description 1
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• 229960003855 solifenacin Drugs 0.000 description 1
• FBOUYBDGKBSUES-VXKWHMMOSA-N solifenacin Chemical compound C1([C@H]2C3=CC=CC=C3CCN2C(O[C@@H]2C3CCN(CC3)C2)=O)=CC=CC=C1 FBOUYBDGKBSUES-VXKWHMMOSA-N 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 238000003797 solvolysis reaction Methods 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 239000012086 standard solution Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 125000001424 substituent group Chemical group 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 229960001940 sulfasalazine Drugs 0.000 description 1
• NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
• NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
• 229960000894 sulindac Drugs 0.000 description 1
• MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
• 210000003863 superior colliculi Anatomy 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 230000007428 synaptic transmission, GABAergic Effects 0.000 description 1
• 108060008037 tachykinin Proteins 0.000 description 1
• 229960004000 talbutal Drugs 0.000 description 1
• BJVVMKUXKQHWJK-UHFFFAOYSA-N talbutal Chemical compound CCC(C)C1(CC=C)C(=O)NC(=O)NC1=O BJVVMKUXKQHWJK-UHFFFAOYSA-N 0.000 description 1
• 229960002613 tamsulosin Drugs 0.000 description 1
• 210000001587 telencephalon Anatomy 0.000 description 1
• 229950000334 temiverine Drugs 0.000 description 1
• 229960003604 testosterone Drugs 0.000 description 1
• 229960002494 tetracaine hydrochloride Drugs 0.000 description 1
• 238000011287 therapeutic dose Methods 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 229960003279 thiopental Drugs 0.000 description 1
• 229960001017 tolmetin Drugs 0.000 description 1
• UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
• 229960004045 tolterodine Drugs 0.000 description 1
• OOGJQPCLVADCPB-HXUWFJFHSA-N tolterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 OOGJQPCLVADCPB-HXUWFJFHSA-N 0.000 description 1
• 208000028500 tonic seizure Diseases 0.000 description 1
• 239000003860 topical agent Substances 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• 229960004394 topiramate Drugs 0.000 description 1
• 231100000816 toxic dose Toxicity 0.000 description 1
• LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 229960003991 trazodone Drugs 0.000 description 1
• PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 description 1
• 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
• 239000008243 triphasic system Substances 0.000 description 1
• 238000001195 ultra high performance liquid chromatography Methods 0.000 description 1
• 229960002004 valdecoxib Drugs 0.000 description 1
• LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
• BDIAUFOIMFAIPU-UHFFFAOYSA-N valepotriate Natural products CC(C)CC(=O)OC1C=C(C(=COC2OC(=O)CC(C)C)COC(C)=O)C2C11CO1 BDIAUFOIMFAIPU-UHFFFAOYSA-N 0.000 description 1
• MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 1
• 229960000604 valproic acid Drugs 0.000 description 1
• 239000000105 vanilloid receptor agonist Substances 0.000 description 1
• 210000005111 ventral hippocampus Anatomy 0.000 description 1
• 229960001255 viloxazine Drugs 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 239000002023 wood Substances 0.000 description 1
• 229960001600 xylazine Drugs 0.000 description 1
• 229960003414 zomepirac Drugs 0.000 description 1
• ZXVNMYWKKDOREA-UHFFFAOYSA-N zomepirac Chemical compound C1=C(CC(O)=O)N(C)C(C(=O)C=2C=CC(Cl)=CC=2)=C1C ZXVNMYWKKDOREA-UHFFFAOYSA-N 0.000 description 1
• LYTCVQQGCSNFJU-LKGYBJPKSA-N α-bungarotoxin Chemical compound C(/[C@H]1O[C@H]2C[C@H]3O[C@@H](CC(=C)C=O)C[C@H](O)[C@]3(C)O[C@@H]2C[C@@H]1O[C@@H]1C2)=C/C[C@]1(C)O[C@H]1[C@@]2(C)O[C@]2(C)CC[C@@H]3O[C@@H]4C[C@]5(C)O[C@@H]6C(C)=CC(=O)O[C@H]6C[C@H]5O[C@H]4C[C@@H](C)[C@H]3O[C@H]2C1 LYTCVQQGCSNFJU-LKGYBJPKSA-N 0.000 description 1