JP6035326B2 - アルツハイマー病、ハンチントン病、自閉症及びその他の疾患を治療する方法 - Google Patents
アルツハイマー病、ハンチントン病、自閉症及びその他の疾患を治療する方法 Download PDFInfo
- Publication number
- JP6035326B2 JP6035326B2 JP2014508130A JP2014508130A JP6035326B2 JP 6035326 B2 JP6035326 B2 JP 6035326B2 JP 2014508130 A JP2014508130 A JP 2014508130A JP 2014508130 A JP2014508130 A JP 2014508130A JP 6035326 B2 JP6035326 B2 JP 6035326B2
- Authority
- JP
- Japan
- Prior art keywords
- glyx
- autism
- disease
- pharmaceutical composition
- rats
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 206010003805 Autism Diseases 0.000 title claims description 45
- 208000020706 Autistic disease Diseases 0.000 title claims description 45
- 208000023105 Huntington disease Diseases 0.000 title claims description 27
- 208000024827 Alzheimer disease Diseases 0.000 title claims description 10
- 238000000034 method Methods 0.000 title description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 14
- 201000010099 disease Diseases 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 57
- GIBQQARAXHVEGD-BSOLPCOYSA-N rapastinel Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)N[C@@H]([C@@H](C)O)C(N)=O)CCC1 GIBQQARAXHVEGD-BSOLPCOYSA-N 0.000 claims description 35
- 108090000623 proteins and genes Proteins 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 9
- 208000024891 symptom Diseases 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 6
- 210000004027 cell Anatomy 0.000 claims description 5
- 230000014509 gene expression Effects 0.000 claims description 4
- 208000000044 Amnesia Diseases 0.000 claims description 3
- 102100029458 Glutamate receptor ionotropic, NMDA 2A Human genes 0.000 claims description 3
- 208000026139 Memory disease Diseases 0.000 claims description 3
- 230000006984 memory degeneration Effects 0.000 claims description 3
- 208000023060 memory loss Diseases 0.000 claims description 3
- 102100035923 4-aminobutyrate aminotransferase, mitochondrial Human genes 0.000 claims description 2
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 claims description 2
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 claims description 2
- 101001000686 Homo sapiens 4-aminobutyrate aminotransferase, mitochondrial Proteins 0.000 claims description 2
- 101001125242 Homo sapiens Glutamate receptor ionotropic, NMDA 2A Proteins 0.000 claims description 2
- 101000745167 Homo sapiens Neuronal acetylcholine receptor subunit alpha-4 Proteins 0.000 claims description 2
- 101001099423 Homo sapiens Proenkephalin-A Proteins 0.000 claims description 2
- 102100039909 Neuronal acetylcholine receptor subunit alpha-4 Human genes 0.000 claims description 2
- 102100038931 Proenkephalin-A Human genes 0.000 claims description 2
- 102100024622 Proenkephalin-B Human genes 0.000 claims description 2
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 claims description 2
- 108010074732 preproenkephalin Proteins 0.000 claims description 2
- WWJZWCUNLNYYAU-UHFFFAOYSA-N temephos Chemical group C1=CC(OP(=S)(OC)OC)=CC=C1SC1=CC=C(OP(=S)(OC)OC)C=C1 WWJZWCUNLNYYAU-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 9
- 101150037123 APOE gene Proteins 0.000 claims 1
- 102100029470 Apolipoprotein E Human genes 0.000 claims 1
- 102000017692 GABRA5 Human genes 0.000 claims 1
- 101001001388 Homo sapiens Gamma-aminobutyric acid receptor subunit alpha-5 Proteins 0.000 claims 1
- 238000010255 intramuscular injection Methods 0.000 claims 1
- 239000007927 intramuscular injection Substances 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 241000700159 Rattus Species 0.000 description 59
- 125000000217 alkyl group Chemical group 0.000 description 22
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 18
- 230000027928 long-term synaptic potentiation Effects 0.000 description 17
- 238000012360 testing method Methods 0.000 description 17
- 230000000694 effects Effects 0.000 description 15
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 14
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 239000008188 pellet Substances 0.000 description 10
- 238000002604 ultrasonography Methods 0.000 description 10
- 239000004471 Glycine Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 125000003342 alkenyl group Chemical group 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 239000004031 partial agonist Substances 0.000 description 8
- 201000000980 schizophrenia Diseases 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 7
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 7
- 206010012335 Dependence Diseases 0.000 description 7
- 150000001413 amino acids Chemical group 0.000 description 7
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 7
- -1 cyano, amino, phenyl Chemical group 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 229910052736 halogen Inorganic materials 0.000 description 7
- 150000002367 halogens Chemical group 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 230000000750 progressive effect Effects 0.000 description 6
- 230000000946 synaptic effect Effects 0.000 description 6
- DYDCUQKUCUHJBH-UWTATZPHSA-N D-Cycloserine Chemical compound N[C@@H]1CONC1=O DYDCUQKUCUHJBH-UWTATZPHSA-N 0.000 description 5
- DYDCUQKUCUHJBH-UHFFFAOYSA-N D-Cycloserine Natural products NC1CONC1=O DYDCUQKUCUHJBH-UHFFFAOYSA-N 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 230000003542 behavioural effect Effects 0.000 description 5
- 238000004891 communication Methods 0.000 description 5
- 206010015037 epilepsy Diseases 0.000 description 5
- 230000000971 hippocampal effect Effects 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 230000005062 synaptic transmission Effects 0.000 description 5
- 208000030507 AIDS Diseases 0.000 description 4
- 208000020925 Bipolar disease Diseases 0.000 description 4
- 206010012289 Dementia Diseases 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 210000005153 frontal cortex Anatomy 0.000 description 4
- 238000010149 post-hoc-test Methods 0.000 description 4
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 3
- 229930195711 D-Serine Natural products 0.000 description 3
- 208000001914 Fragile X syndrome Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000000692 Student's t-test Methods 0.000 description 3
- 208000030886 Traumatic Brain injury Diseases 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 238000009739 binding Methods 0.000 description 3
- 208000010877 cognitive disease Diseases 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 3
- 206010027175 memory impairment Diseases 0.000 description 3
- 238000002493 microarray Methods 0.000 description 3
- 230000016273 neuron death Effects 0.000 description 3
- 210000001009 nucleus accumben Anatomy 0.000 description 3
- 238000001543 one-way ANOVA Methods 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 208000028173 post-traumatic stress disease Diseases 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 210000000225 synapse Anatomy 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 238000012549 training Methods 0.000 description 3
- 230000009529 traumatic brain injury Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 206010054196 Affect lability Diseases 0.000 description 2
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 2
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 2
- 206010008027 Cerebellar atrophy Diseases 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 2
- 208000010496 Heart Arrest Diseases 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000001089 Multiple system atrophy Diseases 0.000 description 2
- 208000036572 Myoclonic epilepsy Diseases 0.000 description 2
- 206010029240 Neuritis Diseases 0.000 description 2
- 206010057852 Nicotine dependence Diseases 0.000 description 2
- 240000007817 Olea europaea Species 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 206010039897 Sedation Diseases 0.000 description 2
- 206010041243 Social avoidant behaviour Diseases 0.000 description 2
- 208000029033 Spinal Cord disease Diseases 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- 208000025569 Tobacco Use disease Diseases 0.000 description 2
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 208000029560 autism spectrum disease Diseases 0.000 description 2
- 206010008129 cerebral palsy Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000008157 edible vegetable oil Substances 0.000 description 2
- 230000002996 emotional effect Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000011670 long-evans rat Methods 0.000 description 2
- 238000013289 male long evans rat Methods 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000002981 neuropathic effect Effects 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 2
- 210000001176 projection neuron Anatomy 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 201000005070 reflex epilepsy Diseases 0.000 description 2
- 230000036280 sedation Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000003956 synaptic plasticity Effects 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 208000009999 tuberous sclerosis Diseases 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- 101150090724 3 gene Proteins 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010052075 Acquired epileptic aphasia Diseases 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 206010063659 Aversion Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000009810 Catatonic Schizophrenia Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 208000003606 Congenital Rubella Syndrome Diseases 0.000 description 1
- 208000024254 Delusional disease Diseases 0.000 description 1
- 208000012239 Developmental disease Diseases 0.000 description 1
- 208000026331 Disruptive, Impulse Control, and Conduct disease Diseases 0.000 description 1
- 201000007547 Dravet syndrome Diseases 0.000 description 1
- 229940124602 FDA-approved drug Drugs 0.000 description 1
- 201000009010 Frontal lobe epilepsy Diseases 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000017605 Hodgkin disease nodular sclerosis Diseases 0.000 description 1
- 101001030705 Homo sapiens Huntingtin Proteins 0.000 description 1
- 101000745175 Homo sapiens Neuronal acetylcholine receptor subunit alpha-5 Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000030990 Impulse-control disease Diseases 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 206010071082 Juvenile myoclonic epilepsy Diseases 0.000 description 1
- 208000005870 Lafora disease Diseases 0.000 description 1
- 208000014161 Lafora myoclonic epilepsy Diseases 0.000 description 1
- 201000005802 Landau-Kleffner Syndrome Diseases 0.000 description 1
- 201000006792 Lennox-Gastaut syndrome Diseases 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 206010061296 Motor dysfunction Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 102100039907 Neuronal acetylcholine receptor subunit alpha-5 Human genes 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- 208000037158 Partial Epilepsies Diseases 0.000 description 1
- 201000011252 Phenylketonuria Diseases 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 206010071141 Rasmussen encephalitis Diseases 0.000 description 1
- 208000004160 Rasmussen subacute encephalitis Diseases 0.000 description 1
- 208000036754 Schizophrenia, catatonic type Diseases 0.000 description 1
- 206010073677 Severe myoclonic epilepsy of infancy Diseases 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- 101100162976 Sus scrofa APOR gene Proteins 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 208000025261 autosomal dominant disease Diseases 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 208000030963 borderline personality disease Diseases 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
- 210000001159 caudate nucleus Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 201000009028 early myoclonic encephalopathy Diseases 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000021824 exploration behavior Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000000499 gel 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
- 230000000848 glutamatergic effect Effects 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 108091008634 hepatocyte nuclear factors 4 Proteins 0.000 description 1
- 102000054185 human HTT Human genes 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 208000034287 idiopathic generalized susceptibility to 7 epilepsy Diseases 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 230000007787 long-term memory Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 208000015015 neurological dysfunction Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 208000002851 paranoid schizophrenia Diseases 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 208000022821 personality disease Diseases 0.000 description 1
- 201000003040 photosensitive epilepsy Diseases 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 210000002637 putamen Anatomy 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003989 repetitive behavior Effects 0.000 description 1
- 208000013406 repetitive behavior Diseases 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 1
- 229960001534 risperidone Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 230000007958 sleep Effects 0.000 description 1
- 230000003997 social interaction Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 208000005809 status epilepticus Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 201000008914 temporal lobe epilepsy Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/07—Tetrapeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Addiction (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Ophthalmology & Optometry (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161479593P | 2011-04-27 | 2011-04-27 | |
| US61/479,593 | 2011-04-27 | ||
| US201161527744P | 2011-08-26 | 2011-08-26 | |
| US61/527,744 | 2011-08-26 | ||
| PCT/US2012/035547 WO2012149389A2 (en) | 2011-04-27 | 2012-04-27 | Methods of treating alzheimer's disease, huntington's disease, autism, or other disorders |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014520072A JP2014520072A (ja) | 2014-08-21 |
| JP2014520072A5 JP2014520072A5 (enExample) | 2016-09-23 |
| JP6035326B2 true JP6035326B2 (ja) | 2016-11-30 |
Family
ID=47073094
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014508130A Expired - Fee Related JP6035326B2 (ja) | 2011-04-27 | 2012-04-27 | アルツハイマー病、ハンチントン病、自閉症及びその他の疾患を治療する方法 |
Country Status (13)
| Country | Link |
|---|---|
| US (4) | US20140107037A1 (enExample) |
| EP (2) | EP2701721A4 (enExample) |
| JP (1) | JP6035326B2 (enExample) |
| KR (5) | KR20200043534A (enExample) |
| CN (2) | CN103974712A (enExample) |
| AU (1) | AU2012249397B2 (enExample) |
| BR (1) | BR112013027554A2 (enExample) |
| CA (1) | CA2834286A1 (enExample) |
| EA (2) | EA201790653A1 (enExample) |
| HK (1) | HK1258231A1 (enExample) |
| MX (1) | MX357761B (enExample) |
| SG (2) | SG194230A1 (enExample) |
| WO (1) | WO2012149389A2 (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5702288B2 (ja) | 2008-09-18 | 2015-04-15 | ノースウエスタン ユニバーシティ | Ｎｍｄａレセプターモジュレータ及びその用途 |
| KR101692275B1 (ko) | 2010-02-11 | 2017-01-04 | 노오쓰웨스턴 유니버시티 | ２차 구조 안정화된 ｎｍｄａ 수용체 조절제 및 그의 용도 |
| SG183265A1 (en) | 2010-02-11 | 2012-09-27 | Univ Northwestern | Secondary structure stabilized nmda receptor modulators and uses thereof |
| CA2899191A1 (en) | 2013-01-29 | 2014-08-07 | Naurex, Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| PE20151437A1 (es) | 2013-01-29 | 2015-10-10 | Naurex Inc | Moduladores de receptores nmda de espiro-lactama y sus usos |
| KR20150110586A (ko) | 2013-01-29 | 2015-10-02 | 노렉스, 인크. | 스피로-락탐 nmda 수용체 조절인자 및 그의 용도 |
| LT3514158T (lt) | 2013-01-29 | 2023-02-10 | Aptinyx Inc. | Spirolaktaminiai nmda receptoriaus moduliatoriai ir jų panaudojimas |
| PH12015501596B1 (en) | 2013-01-29 | 2023-12-06 | Aptinyx Inc | Spiro-lactam nmda receptor modulators and uses thereof |
| WO2015065891A1 (en) * | 2013-10-28 | 2015-05-07 | Naurex, Inc. | Nmda receptor modulators and prodrugs, salts, and uses thereof |
| CN111920412A (zh) * | 2013-12-13 | 2020-11-13 | 西北大学 | 治疗脑部病症或鉴定与其相关的生物标记的方法 |
| CN105327349A (zh) * | 2014-06-18 | 2016-02-17 | 上海翰森生物医药科技有限公司 | Nmda受体拮抗剂的医药用途及其药物组合物 |
| KR20170018072A (ko) * | 2014-06-23 | 2017-02-15 | 노오쓰웨스턴 유니버시티 | 편두통을 치료 또는 경감시키는 방법 |
| JP2018530593A (ja) * | 2015-10-16 | 2018-10-18 | ノースウェスタン ユニバーシティ | 統合失調症、双極性障害、認知障害及び大うつ病性障害の治療のための非定型的抗精神病薬ならびにｎｍｄａ調節剤の医薬品の組み合わせ |
| CN109415372B (zh) | 2016-05-19 | 2021-01-15 | 阿普廷伊克斯股份有限公司 | 螺-内酰胺nmda受体调节剂及其用途 |
| WO2017201285A1 (en) | 2016-05-19 | 2017-11-23 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| ES2974090T3 (es) | 2016-08-01 | 2024-06-25 | Tenacia Biotechnology Hong Kong Co Ltd | Moduladores de NMDA de espirolactama y métodos de uso de los mismos |
| MX383292B (es) | 2016-08-01 | 2025-03-13 | Aptinyx Inc | Moduladores del receptor nmda spiro-lactam y bis-spiro-lactam y uso de los mismos. |
| KR102465758B1 (ko) | 2016-08-01 | 2022-11-09 | 앱티닉스 인크. | 스피로-락탐 nmda 수용체 조정제 및 그의 용도 |
| EA201990428A1 (ru) | 2016-08-01 | 2019-08-30 | Аптиникс Инк. | Спиролактамовые модуляторы nmda-рецептора и их применение |
| PE20190500A1 (es) | 2016-08-01 | 2019-04-10 | Aptinyx Inc | Moduladores del receptor nmda spiro-lactam y uso de los mismos |
| ES3008466T3 (en) | 2018-01-31 | 2025-03-24 | Tenacia Biotechnology Hong Kong Co Ltd | Spiro-lactam nmda receptor modulators and uses thereof |
| US12012413B2 (en) | 2019-11-11 | 2024-06-18 | Tenacia Biotechnology (Hong Kong) Co., Limited | Methods of treating painful diabetic peripheral neuropathy |
| KR102415692B1 (ko) | 2020-09-01 | 2022-07-05 | 건국대학교 글로컬산학협력단 | 시냅스 불균형 조절에 의한 발달장애 예방, 개선 또는 치료용 조성물 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4086196A (en) | 1975-03-28 | 1978-04-25 | Armour Pharmaceutical Company | Parathyroid hormone |
| US5763393A (en) | 1996-05-17 | 1998-06-09 | Neurotherapeutics L.P. | Neuroactive peptides |
| GB0018272D0 (en) * | 2000-07-25 | 2000-09-13 | Vernalis Research Limited | Chemical compounds IV |
| AU2003210486B2 (en) * | 2002-01-16 | 2007-06-28 | Endo Pharmaceuticals Inc. | Pharmaceutical composition and method for treating disorders of the central nervous system |
| US20060063707A1 (en) * | 2004-09-17 | 2006-03-23 | Lifelike Biomatic, Inc. | Compositions for enhancing memory and methods therefor |
| EP2030622B1 (en) * | 2005-03-24 | 2011-02-23 | Emory University | Indication of dosage of progesterone in the treatment of a traumatic brain injury |
| AU2009217278B2 (en) * | 2008-02-20 | 2015-08-20 | The Children's Hospital Of Philadelphia | Genetic alterations associated with autism and the autistic phenotype and methods of use thereof for the diagnosis and treatment of autism |
| JP5702288B2 (ja) * | 2008-09-18 | 2015-04-15 | ノースウエスタン ユニバーシティ | Ｎｍｄａレセプターモジュレータ及びその用途 |
| EP3488856A1 (en) * | 2009-10-05 | 2019-05-29 | Northwestern University | Methods of treating depression and other related diseases |
-
2012
- 2012-04-27 EP EP12777016.2A patent/EP2701721A4/en not_active Ceased
- 2012-04-27 WO PCT/US2012/035547 patent/WO2012149389A2/en not_active Ceased
- 2012-04-27 KR KR1020207011211A patent/KR20200043534A/ko not_active Ceased
- 2012-04-27 EP EP20151676.2A patent/EP3679931A3/en not_active Withdrawn
- 2012-04-27 CN CN201280027349.3A patent/CN103974712A/zh active Pending
- 2012-04-27 US US14/114,376 patent/US20140107037A1/en not_active Abandoned
- 2012-04-27 MX MX2013012526A patent/MX357761B/es active IP Right Grant
- 2012-04-27 CA CA2834286A patent/CA2834286A1/en not_active Abandoned
- 2012-04-27 KR KR1020137031028A patent/KR20140043078A/ko not_active Ceased
- 2012-04-27 EA EA201790653A patent/EA201790653A1/ru unknown
- 2012-04-27 JP JP2014508130A patent/JP6035326B2/ja not_active Expired - Fee Related
- 2012-04-27 SG SG2013079603A patent/SG194230A1/en unknown
- 2012-04-27 KR KR1020197008907A patent/KR20190037359A/ko not_active Ceased
- 2012-04-27 EA EA201391581A patent/EA029999B1/ru unknown
- 2012-04-27 AU AU2012249397A patent/AU2012249397B2/en not_active Ceased
- 2012-04-27 CN CN201711451914.XA patent/CN108283712A/zh active Pending
- 2012-04-27 SG SG10202010665YA patent/SG10202010665YA/en unknown
- 2012-04-27 KR KR1020187022910A patent/KR20180095096A/ko not_active Ceased
- 2012-04-27 KR KR1020217011613A patent/KR20210046843A/ko not_active Ceased
- 2012-04-27 BR BR112013027554A patent/BR112013027554A2/pt not_active Application Discontinuation
-
2016
- 2016-04-14 US US15/098,985 patent/US20170049845A1/en not_active Abandoned
-
2018
- 2018-10-23 US US16/168,242 patent/US20190209642A1/en not_active Abandoned
-
2019
- 2019-01-14 HK HK19100591.2A patent/HK1258231A1/zh unknown
-
2020
- 2020-05-05 US US16/867,324 patent/US20210169964A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| SG10202010665YA (en) | 2020-11-27 |
| CA2834286A1 (en) | 2012-11-01 |
| WO2012149389A3 (en) | 2014-05-08 |
| AU2012249397B2 (en) | 2017-03-30 |
| US20170049845A1 (en) | 2017-02-23 |
| CN103974712A (zh) | 2014-08-06 |
| EP2701721A2 (en) | 2014-03-05 |
| EA201391581A1 (ru) | 2014-05-30 |
| MX357761B (es) | 2018-07-23 |
| KR20200043534A (ko) | 2020-04-27 |
| CN108283712A (zh) | 2018-07-17 |
| KR20180095096A (ko) | 2018-08-24 |
| HK1258231A1 (zh) | 2019-11-08 |
| WO2012149389A2 (en) | 2012-11-01 |
| US20210169964A1 (en) | 2021-06-10 |
| EP2701721A4 (en) | 2015-12-16 |
| KR20140043078A (ko) | 2014-04-08 |
| MX2013012526A (es) | 2014-04-16 |
| JP2014520072A (ja) | 2014-08-21 |
| EP3679931A2 (en) | 2020-07-15 |
| KR20190037359A (ko) | 2019-04-05 |
| EA201790653A1 (ru) | 2017-07-31 |
| US20190209642A1 (en) | 2019-07-11 |
| US20140107037A1 (en) | 2014-04-17 |
| EA029999B1 (ru) | 2018-06-29 |
| AU2012249397A1 (en) | 2013-11-07 |
| BR112013027554A2 (pt) | 2016-09-06 |
| EP3679931A3 (en) | 2020-10-14 |
| KR20210046843A (ko) | 2021-04-28 |
| SG194230A1 (en) | 2013-12-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6035326B2 (ja) | アルツハイマー病、ハンチントン病、自閉症及びその他の疾患を治療する方法 | |
| Cevikbas et al. | Physiology and pathophysiology of itch | |
| CN108024976A (zh) | 阿米替林用于阻断大脑半通道的用途和用于增强其体内作用的方法 | |
| JP2013542266A (ja) | 認知障害を処置するためのベンゾジアゼピン誘導体、組成物、および方法 | |
| WO2022215080A1 (en) | A combined use of ketamine and retigabine (ezogabine) for the treatment of psychiatric disorders | |
| JP2003508512A (ja) | 非ペプチド性サイクロフィリン結合化合物とその用途 | |
| Mir et al. | Proton pump inhibitor “Lansoprazole” inhibits locus coeruleus’s neuronal activity and increases rapid eye movement sleep | |
| EP3797097A1 (en) | Compositions and methods for reducing tactile dysfunction, anxiety, and social impairment | |
| CN115463218B (zh) | Shh通路调控生物节律及其相关应用 | |
| Xie et al. | Orally bioavailable prodrugs of ψ-GSH: a potential treatment for Alzheimer’s disease | |
| EP4554629A1 (en) | Methods and formulations for gene therapy, and for combining gene therapy with ditpa treatment, of allan-herndon-dudley syndrome | |
| JPH10508579A (ja) | シナプス伝達を改善する薬 | |
| Hiramatsu et al. | Dynorphin A (2-13) improves mecamylamine-induced learning impairment accompanied by reversal of reductions in acetylcholine release in rats | |
| EP3607948A1 (en) | Tissue transglutaminase modulators for medicinal use | |
| US20090221610A1 (en) | Compositions and Methods for Treating Cognitive Disorders | |
| HK40034037A (en) | Methods of treating alzheimer's disease, huntington's disease, autism, and other disorders | |
| KR102640789B1 (ko) | 질소 함유 헤테로고리 화합물 및 그의 용도 | |
| JP2009132672A (ja) | ボツリヌス毒素由来のポリペプチドを有効成分として含む鎮痛作用を有する医薬組成物 | |
| TW200920364A (en) | Method for reducing amyloid deposition, amyloid neurotoxicity, and microgliosis with (-)-nilvadipine enantiomer | |
| FR3163835A1 (fr) | Derives de fluoroethylnormemantine | |
| CA3247785A1 (en) | USE OF 5-HT1A SEROTONIN RECEPTOR AGONISTS TO TREAT DISEASES ASSOCIATED WITH SUDDEN UNSURPRISED DEATH IN EPILEPSY | |
| WO2026003229A1 (fr) | Derives de fluoroethylnormemantine pour leur utilisation en tant que medicament | |
| Class et al. | Patent application title: METHODS TO REDUCE THE EFFECTS OF SLEEP DEPRIVATION Inventors: Samuel A. Deadwyler (Lewisville, NC, US) Robert E. Hampson (Kernersville, NC, US) Linda Porrino (Lewisville, NC, US) Michael Todd (Winston Salem, NC, US) Thomas N. Thannickal (Winnetka, CA, US) Yuan-Yan Lai (North Hills, CA, US) Jerome M. Siegel (Northridge, CA, US) Assignees: The US Government Respresented by the Department of Veterans Affairs | |
| Kukko-Lukjanov | The central histaminergic neurons in vitro, and their neuroprotective role in excitotoxic cell death in the postnatal rat hippocampus. | |
| FR3057266A1 (fr) | Peptides derives du propeptide ntsr3 et leur utilisation dans le traitement de la depression |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150421 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150421 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160126 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160331 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20160413 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20160513 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20160513 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160627 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160726 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20160726 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20161003 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20161031 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6035326 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |