JP2009167205A - グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置 - Google Patents
グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置 Download PDFInfo
- Publication number
- JP2009167205A JP2009167205A JP2009066534A JP2009066534A JP2009167205A JP 2009167205 A JP2009167205 A JP 2009167205A JP 2009066534 A JP2009066534 A JP 2009066534A JP 2009066534 A JP2009066534 A JP 2009066534A JP 2009167205 A JP2009167205 A JP 2009167205A
- Authority
- JP
- Japan
- Prior art keywords
- glycine
- treatment
- symptoms
- capture
- schizophrenia
- 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.)
- Granted
Links
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 title claims abstract description 423
- 239000004471 Glycine Substances 0.000 title claims abstract description 212
- 201000000980 schizophrenia Diseases 0.000 title claims abstract description 42
- 239000005557 antagonist Substances 0.000 title claims abstract description 27
- 238000011282 treatment Methods 0.000 title abstract description 82
- 208000009668 Neurobehavioral Manifestations Diseases 0.000 title description 5
- 238000000034 method Methods 0.000 claims abstract description 23
- 230000001404 mediated effect Effects 0.000 claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 21
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 20
- 230000005062 synaptic transmission Effects 0.000 claims abstract description 18
- 239000003176 neuroleptic agent Substances 0.000 claims abstract description 10
- 230000000561 anti-psychotic effect Effects 0.000 claims abstract description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 3
- 208000020925 Bipolar disease Diseases 0.000 claims abstract description 3
- 239000003368 psychostimulant agent Substances 0.000 claims abstract description 3
- 208000028683 bipolar I disease Diseases 0.000 claims abstract 2
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 28
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 28
- 229940079593 drug Drugs 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 102100022622 Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase Human genes 0.000 claims description 6
- 101000972916 Homo sapiens Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase Proteins 0.000 claims description 6
- 101000856513 Homo sapiens Inactive N-acetyllactosaminide alpha-1,3-galactosyltransferase Proteins 0.000 claims description 5
- 102100025509 Inactive N-acetyllactosaminide alpha-1,3-galactosyltransferase Human genes 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 230000000701 neuroleptic effect Effects 0.000 claims description 4
- 230000001737 promoting effect Effects 0.000 claims description 3
- 206010013663 drug dependence Diseases 0.000 claims description 2
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 2
- 208000011117 substance-related disease Diseases 0.000 claims description 2
- 230000003444 anaesthetic effect Effects 0.000 claims 1
- 208000024891 symptom Diseases 0.000 abstract description 69
- 208000011580 syndromic disease Diseases 0.000 abstract description 12
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 abstract description 6
- 239000003372 dissociative anesthetic agent Substances 0.000 abstract description 2
- 102000005962 receptors Human genes 0.000 abstract description 2
- 108020003175 receptors Proteins 0.000 abstract description 2
- 231100000643 Substance intoxication Toxicity 0.000 abstract 1
- 206010070863 Toxicity to various agents Diseases 0.000 abstract 1
- 208000024714 major depressive disease Diseases 0.000 abstract 1
- 230000003389 potentiating effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 65
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 56
- 239000000902 placebo Substances 0.000 description 26
- 229940068196 placebo Drugs 0.000 description 26
- 230000006872 improvement Effects 0.000 description 23
- 210000004556 brain Anatomy 0.000 description 21
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 17
- 230000009467 reduction Effects 0.000 description 16
- 230000000698 schizophrenic effect Effects 0.000 description 16
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 14
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 13
- 229940025084 amphetamine Drugs 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 11
- 241000283984 Rodentia Species 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 10
- 208000013403 hyperactivity Diseases 0.000 description 10
- 230000002401 inhibitory effect Effects 0.000 description 10
- 238000003556 assay Methods 0.000 description 9
- 230000008859 change Effects 0.000 description 9
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 108010077895 Sarcosine Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000000164 antipsychotic agent Substances 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 7
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 229950010883 phencyclidine Drugs 0.000 description 7
- 229940043230 sarcosine Drugs 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- UMHNKSKNRHLEEW-UHFFFAOYSA-N 1,14-diaminotetradecan-2-one Chemical compound NCCCCCCCCCCCCC(=O)CN UMHNKSKNRHLEEW-UHFFFAOYSA-N 0.000 description 5
- 102000010726 Glycine Plasma Membrane Transport Proteins Human genes 0.000 description 5
- 108010063380 Glycine Plasma Membrane Transport Proteins Proteins 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 230000006399 behavior Effects 0.000 description 5
- 230000003542 behavioural effect Effects 0.000 description 5
- 229960004170 clozapine Drugs 0.000 description 5
- 229960003638 dopamine Drugs 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 229930195712 glutamate Natural products 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 108010078791 Carrier Proteins Proteins 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 229940005529 antipsychotics Drugs 0.000 description 4
- 208000010877 cognitive disease Diseases 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- SEJVQOMVWXKDMS-UHFFFAOYSA-N 1,8-diaminooctan-2-one Chemical compound NCCCCCCC(=O)CN SEJVQOMVWXKDMS-UHFFFAOYSA-N 0.000 description 3
- 208000028698 Cognitive impairment Diseases 0.000 description 3
- 208000027776 Extrapyramidal disease Diseases 0.000 description 3
- 108010063843 Phencyclidine Receptors Proteins 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 230000001149 cognitive effect Effects 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 3
- 238000000556 factor analysis Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 3
- 150000002332 glycine derivatives Chemical class 0.000 description 3
- 229960003878 haloperidol Drugs 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229960001534 risperidone Drugs 0.000 description 3
- 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 3
- 238000007619 statistical method Methods 0.000 description 3
- NRSBQSJHFYZIPH-DMTCNVIQSA-N (2s,4r)-pyrrolidine-2,4-dicarboxylic acid Chemical compound OC(=O)[C@H]1CN[C@H](C(O)=O)C1 NRSBQSJHFYZIPH-DMTCNVIQSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- IZWUORPLOVCIJU-UHFFFAOYSA-N 2-(2-aminoacetyl)undecanamide Chemical compound CCCCCCCCCC(C(N)=O)C(=O)CN IZWUORPLOVCIJU-UHFFFAOYSA-N 0.000 description 2
- 206010010144 Completed suicide Diseases 0.000 description 2
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 2
- 229930195711 D-Serine Natural products 0.000 description 2
- 206010054089 Depressive symptom Diseases 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- NRSBQSJHFYZIPH-UHFFFAOYSA-N L-trans-PDC Natural products OC(=O)C1CNC(C(O)=O)C1 NRSBQSJHFYZIPH-UHFFFAOYSA-N 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- HWHLPVGTWGOCJO-UHFFFAOYSA-N Trihexyphenidyl Chemical group C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 HWHLPVGTWGOCJO-UHFFFAOYSA-N 0.000 description 2
- 208000003443 Unconsciousness Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 210000000133 brain stem Anatomy 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960001076 chlorpromazine Drugs 0.000 description 2
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000007012 clinical effect Effects 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
- 230000001054 cortical effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 230000008451 emotion Effects 0.000 description 2
- 230000002964 excitative effect Effects 0.000 description 2
- 230000005021 gait Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 210000003568 synaptosome Anatomy 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229960001032 trihexyphenidyl Drugs 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 description 1
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000017194 Affective disease Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- DYDCUQKUCUHJBH-UWTATZPHSA-N D-Cycloserine Chemical compound N[C@@H]1CONC1=O DYDCUQKUCUHJBH-UWTATZPHSA-N 0.000 description 1
- DYDCUQKUCUHJBH-UHFFFAOYSA-N D-Cycloserine Natural products NC1CONC1=O DYDCUQKUCUHJBH-UHFFFAOYSA-N 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 229940121891 Dopamine receptor antagonist Drugs 0.000 description 1
- 208000035859 Drug effect increased Diseases 0.000 description 1
- PLDUPXSUYLZYBN-UHFFFAOYSA-N Fluphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 PLDUPXSUYLZYBN-UHFFFAOYSA-N 0.000 description 1
- 206010060891 General symptom Diseases 0.000 description 1
- 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 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 235000005135 Micromeria juliana Nutrition 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 229940095474 NMDA agonist Drugs 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- KNTFCRCCPLEUQZ-VKHMYHEASA-N O-methylserine Chemical compound COC[C@H](N)C(O)=O KNTFCRCCPLEUQZ-VKHMYHEASA-N 0.000 description 1
- 241000246354 Satureja Species 0.000 description 1
- 235000007315 Satureja hortensis Nutrition 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 208000031555 Treatment-Resistant Schizophrenia Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229940125516 allosteric modulator Drugs 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000001090 anti-dopaminergic effect Effects 0.000 description 1
- 229940035678 anti-parkinson drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 239000003693 atypical antipsychotic agent Substances 0.000 description 1
- 229940127236 atypical antipsychotics Drugs 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 235000021152 breakfast Nutrition 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 229940068796 clozaril Drugs 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 210000003618 cortical neuron Anatomy 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 210000002451 diencephalon Anatomy 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000003492 excitotoxic effect Effects 0.000 description 1
- 231100000063 excitotoxicity Toxicity 0.000 description 1
- 229960002690 fluphenazine Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229940095895 haldol Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000009592 kidney function test Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000007449 liver function test Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001459 mortal effect Effects 0.000 description 1
- 230000001095 motoneuron effect Effects 0.000 description 1
- 239000003706 n methyl dextro aspartic acid receptor stimulating agent Substances 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000000956 olfactory bulb Anatomy 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 208000022821 personality disease Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940117953 phenylisothiocyanate Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 238000001121 post-column derivatisation Methods 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000003196 psychodysleptic agent Substances 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000015883 synaptic transmission, dopaminergic Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 229960002784 thioridazine Drugs 0.000 description 1
- 230000001550 time effect Effects 0.000 description 1
- 208000029252 treatment-refractory schizophrenia Diseases 0.000 description 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Toxicology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
【解決手段】精神病と精神分裂病の症候群の処置のために、該症候群で患う患者に対して、NMDA(N−メチル−D−アスパルテート)レセプター仲介神経伝達を促進するのに十分な量のグリシン捕捉アンタゴニスト、更には抗精神病薬である神経弛緩薬が投与される。
【選択図】なし
Description
本発明は、グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置に関する。
本発明が解決しようとする課題は、新規なNMDAレセプター仲介神経伝達を促進させる方法を提供することである。
方法:この研究はブロンクス(ニューヨーク)にあるブロンクス・精神病センターにおいておこなわれた。インフォームド・コンセントを得た後でこの研究に参加してあらかじめ二重盲検法においてグリシンを0.4g/kg/日の割合で投与された5人の精神分裂病患者(DSM−IV)を採用した。患者の平均年令は45.0±7.6才であり、慢性的な平均病歴は24.2±5.9年であった。いずれの患者も重度の病状を示した(CG1>4)。すべての患者には試験の少なくとも4週間前から抗精神病薬(クロザピン2、リペリドン2およびハロペリドール1)を投与した。
結果:グリシンの経口投与による処置によってグリシンの血中濃度は著しく増加し(6.3倍)、この値は2〜6週にわたって安定に維持された(図1参照)。6〜8週にかけては統計的に意義のある程度ではないが、グリシンの血中濃度に明らかな低下がみられた。8週間の試験期間中には不都合な効果、例えば衰弱、嘔気および鎮静はみられなかった。SANSを用いたときには拒絶性症候において著しい改善効果がみられた(ベースライン:75.8±7.2、試験後: 72.2±8.6、t=2.79、p=0.049)。一方、PANSSを用いたときには拒絶性症候において改善傾向がみられた(ベースライン:31.0±2.3、試験後: 27.4±3.2、t=2.21、p=0.092)。5人のうちの2人の患者においては拒絶性症候において20%以上の低減効果がみられた。処置応答と全患者のグリシン濃度または個々の患者のグリシン濃度の経時変化との間には著しい関連性はみられなかった。
方法:被験者としてはサラー・ヘルツォグ記念病院の研究病棟(エルサレム、イスラエル)の入院患者を採用した。これらの患者はDSM−III−R(米国精神医学協会、1987年)の精神分裂病と診断されていた。さらに、これらの患者は従来の神経弛緩薬に対する応答が弱いために抗療性があるとみなされていた。試験を開始する前に、少なくとも3カ月間にわたって常套の神経弛緩薬またはクロザピンを臨床的に最適な投与量でこれらの患者に定期的に経口投与した。付加的なDSM−III−R診断を受けた精神分裂病患者の場合には付加的な向精神薬もしくは併用薬を投与するか、または神経学的症状を解消させた。12人の患者をこの研究においては採用した。全ての患者からはこの研究に参加することについて書面によるインフォームド・コンセントを得た。また、この研究は病院の審査委員会の認可を受けた。
PANSSの伝統的分析法においては、症候は従命自動性症候、拒絶性症候および一般的症候に分類されるが、5因子または7因子を組み込む別の分析法が提案されている。5因子モデルによれば症候は従命自動性のもの、拒絶性のもの、認知性のもの、うつ病性のもの、および興奮性のものに分類される。従命自動性および拒絶性症候以外の精神分裂病の程度に及ぼすグリシンの影響度を測定するために、5因子成分を用いてデータの二次分析をおこなった(図4参照)。3因子分析の場合のように、PANSS従命自動性症候に関してはグリシンまたはプラセボ処置中においては著しい低減効果はみられなかったが、プラセボ処置期間ではなくてグリシン処置期間においては著しく漸進的な改善効果がみられた[経時処置F(3,8)=19.5、p<0.0001]。しかしながら、5因子分析法によれば、うつ症候[F(3,8)=7.23、p<0.02]および認知性症候[F(3,8)=4.74、p<0.05]に対しても著しい低減効果がみられた。うつ症候[F(3,5)=2.13、p=0.22]に対しても著しい認知性症候[F(3,5)=0.89、p=0.51]における改善効果は拒絶性症候における変化に対する共変によって維持されなかった。
グリシルドデシルアミド(GDA)は1986年の非特許文献20に最初に報告されたグリシン誘導体である。当時、この化合物はPCP誘発機能高進の転換に関してはグリシンよりも著しく高い効能をもたらすことが示された。さらに、GDAの投与によって脳内の全グリシン濃度は増加しないことが示され、このことはGDAがグリシンの前駆体として作用しなかったことを示す。当時、PCP誘発機能高進に対するGDA誘発抑制機構は仮定されていなかった。
Claims (12)
- NMDAレセプター仲介神経伝達を促進するのに十分な量のグリシン捕捉アンタゴニストをヒトに投与することを含む、ヒトにおけるNMDAレセプター仲介神経伝達促進法。
- 精神病で患うヒトの患者に、NMDAレセプター仲介神経伝達を促進するのに十分な量のグリシン捕捉アンタゴニストを該患者に投与することを含む該患者の処置法。
- 精神病が病気と関連する請求項2記載の方法。
- 病気が重度のうつ病、躁うつ病、アルツハイマー病または外傷後ストレス症である請求項2記載の方法。
- 精神病が薬物中毒と関連する請求項2記載の方法。
- 薬物が解離性麻酔薬または精神刺激薬である請求項5記載の方法。
- 精神分裂病で患うヒトの患者にNMDAレセプター仲介神経伝達を促進するのに十分な量のグリシン捕捉アンタゴニストを投与することを含む精神分裂病の処置法。
- 抗精神病薬も患者に投与する請求項7記載の方法。
- 抗精神病薬が神経弛緩薬である請求項8記載の方法。
- GLYT1またはGLYT2仲介グリシン捕捉が抑制される請求項1記載の方法。
- GLYT1またはGLYT2仲介グリシン捕捉が抑制される請求項2記載の方法。
- GLYT1またはGLYT2仲介グリシン捕捉が抑制される請求項7記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US836195P | 1995-12-07 | 1995-12-07 | |
US60/008,361 | 1995-12-07 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP09521348A Division JP2000501707A (ja) | 1995-12-07 | 1996-12-05 | グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012251233A Division JP2013056918A (ja) | 1995-12-07 | 2012-11-15 | グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2009167205A true JP2009167205A (ja) | 2009-07-30 |
JP5363152B2 JP5363152B2 (ja) | 2013-12-11 |
Family
ID=21731199
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP09521348A Pending JP2000501707A (ja) | 1995-12-07 | 1996-12-05 | グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置 |
JP2009066534A Expired - Fee Related JP5363152B2 (ja) | 1995-12-07 | 2009-03-18 | グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置 |
JP2012251233A Pending JP2013056918A (ja) | 1995-12-07 | 2012-11-15 | グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP09521348A Pending JP2000501707A (ja) | 1995-12-07 | 1996-12-05 | グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012251233A Pending JP2013056918A (ja) | 1995-12-07 | 2012-11-15 | グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置 |
Country Status (10)
Country | Link |
---|---|
US (3) | US5837730A (ja) |
EP (1) | EP0871440B1 (ja) |
JP (3) | JP2000501707A (ja) |
AT (1) | ATE320804T1 (ja) |
DE (1) | DE69635959T2 (ja) |
DK (1) | DK0871440T3 (ja) |
ES (1) | ES2260773T3 (ja) |
IL (1) | IL124536A (ja) |
PT (1) | PT871440E (ja) |
WO (2) | WO1997020553A1 (ja) |
Families Citing this family (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6361957B1 (en) | 1999-08-03 | 2002-03-26 | Glytech, Inc. | Assay for D-serine transport antagonist and use for treating psychosis |
US6355681B2 (en) * | 1995-12-07 | 2002-03-12 | Glytech, Inc. | Glycine substitutes and precursors for treating a psychosis |
WO1997020553A1 (en) * | 1995-12-07 | 1997-06-12 | Javitt Daniel C | Treatment of negative and cognitive symptoms of schizophrenia with glycine uptake antagonists |
US6191165B1 (en) | 1996-05-31 | 2001-02-20 | Allelix Neuroscience Inc. | Pharmaceutical for treatment of neurological and neuropsychiatric disorders |
US6001854A (en) * | 1996-05-31 | 1999-12-14 | Allelix Neuroscience Inc. | Pharmaceutical for treating of neurological and neuropsychiatric disorders |
EP2338482A3 (en) * | 1998-04-14 | 2011-12-21 | The General Hospital Corporation | Methods for treating neuropsychiatric disorders |
US6416975B1 (en) * | 1998-11-12 | 2002-07-09 | Gliatech, Inc. | Human glycine transporter type 2 |
WO2000062812A1 (en) * | 1999-04-20 | 2000-10-26 | Advocare International Llc | Nutritional composition for improved cognitive performance |
US6551993B1 (en) * | 1999-08-16 | 2003-04-22 | Thomas Jefferson University | Partial agonists at the glycine modulatory site of the NMDA receptor for treating cognitive dysfunction |
UA73749C2 (en) * | 1999-11-01 | 2005-09-15 | Diarylenines | |
TWI243173B (en) | 1999-11-17 | 2005-11-11 | Akzo Nobel Nv | Spiro[2H-1-benzopyran-2,4'-piperidine] derivatives |
PL365024A1 (en) | 2001-02-16 | 2004-12-27 | Allelix Neuroscience, Inc. | Thiophene substituted amine derivatives as glyt-1 inhibitors |
US20020187544A1 (en) * | 2001-04-05 | 2002-12-12 | Wisconsin Alumni Research Foundation | Uropathogenic E. coli D-serine detoxification operon |
JP4299243B2 (ja) * | 2002-07-04 | 2009-07-22 | 田辺三菱製薬株式会社 | 統合失調症の検査、診断方法 |
FR2843590B1 (fr) * | 2002-08-14 | 2007-10-05 | Prestwick Scient Capital Inc | Derives de l'acide r(+)-2-amino-3-hydroxypropanoique a action glycinergique |
US7160913B2 (en) * | 2002-09-13 | 2007-01-09 | Thomas Jefferson University | Methods and kit for treating Parkinson's disease |
KR101095939B1 (ko) * | 2003-01-16 | 2011-12-19 | 아카디아 파마슈티칼스 인코포레이티드 | 신경퇴행성 질환에 대한 치료제로서 선택적 세로토닌2a/2c 리셉터 역작용제 |
IL154318A (en) | 2003-02-06 | 2010-05-31 | Sarah Herzog Memorial Hospital | Pharmaceutical compositions for the treatment of movement disorders |
KR20060004967A (ko) | 2003-04-30 | 2006-01-16 | 하. 룬트벡 아크티에 셀스카브 | 방향족 옥시페닐 및 방향족 설파닐페닐 유도체 |
CN1867358A (zh) * | 2003-08-21 | 2006-11-22 | H.隆德贝克有限公司 | 用于治疗抑郁症的5-羟色胺再摄取抑制剂和1型甘氨酸转运蛋白抑制剂的联合药物 |
US20070270403A1 (en) * | 2003-12-04 | 2007-11-22 | Broderick Patricia A | Clozapine and Cocaine Effects on Dopamine and Serotonin Release in Nucleus Accumbens During Psychostimulant Behavior and Withdrawal |
EP1781279A2 (de) * | 2004-06-11 | 2007-05-09 | Egon Tech | Präparat zur prophylaxe und therapie von stresszuständen, von funktionellen und organischen störungen des nervensystems und des stoffwechsels |
WO2006000222A2 (en) * | 2004-06-24 | 2006-01-05 | H. Lundbeck A/S | The combination of an antipsychotic and a glycine transporter type i inhibitor for the treatment of schizophrenia |
CA2579962A1 (en) | 2004-08-09 | 2006-06-01 | Enrique Melendez Hevia | Glycine as a diet supplement for the treatment of health problems that result from underlying metabolic disorders |
PT1830833E (pt) * | 2004-12-16 | 2010-03-12 | Janssen Pharmaceutica Nv | Combinação de um inibidor do transportador da glicina (glyt1) e um antipsicótico para o tratamento de sintomas de esquizofrenia, bem como a sua preparação e sua utilização |
WO2008013860A2 (en) * | 2006-07-28 | 2008-01-31 | Xenoport, Inc. | Acyloxyalkyl carbamate prodrugs of alpha-amino acids, methods of synthesis and use |
DK2134330T3 (da) | 2007-03-19 | 2013-08-05 | Acadia Pharm Inc | Kominationer af 5-ht2a-inverse agonister og antagonister med antipsykotika |
EP2200610B1 (en) * | 2007-09-21 | 2018-01-10 | Acadia Pharmaceuticals Inc. | Co-administration of pimavanserin with other agents |
IL188681A0 (en) * | 2008-01-09 | 2008-12-29 | Amino Acid Solutions Inc | Pharmaceutical compositions and methods utilizing a d-amino acid |
US20110263968A1 (en) * | 2008-11-04 | 2011-10-27 | Mclean Hospital Corporation | Drug-Enhanced Neurofeedback |
US8951968B2 (en) | 2009-10-05 | 2015-02-10 | Northwestern University | Methods of treating depression and other related diseases |
WO2012065102A2 (en) * | 2010-11-12 | 2012-05-18 | Promentis Pharmaceuticals, Inc. | S-t-butyl protected cysteine di-peptide analogs and related compounds |
US9737531B2 (en) | 2012-07-12 | 2017-08-22 | Glytech, Llc | Composition and method for treatment of depression and psychosis in humans |
PT3325444T (pt) | 2015-07-20 | 2021-09-22 | Acadia Pharm Inc | Métodos para preparar n-(4-fluorobenzil)-n-(1-metilpiperidina-4-il)-n'-(4-(2-metilpropiloxi)fenilmetil)carbamida e o seu sal de tartarato e forma polimórfica c |
US10953000B2 (en) | 2016-03-25 | 2021-03-23 | Acadia Pharmaceuticals Inc. | Combination of pimavanserin and cytochrome P450 modulators |
WO2017165635A1 (en) | 2016-03-25 | 2017-09-28 | Acadia Pharmaceuticals Inc. | Combination of pimavanserin and cytochrome p450 modulators |
EP3558311A1 (en) | 2016-12-20 | 2019-10-30 | Acadia Pharmaceuticals Inc. | Pimavanserin alone or in combination for use in the treatment of alzheimer's disease psychosis |
US11135211B2 (en) | 2017-04-28 | 2021-10-05 | Acadia Pharmaceuticals Inc. | Pimavanserin for treating impulse control disorder |
RU2020100230A (ru) | 2017-06-12 | 2021-07-13 | Глитек Ллс. | Лечение депрессии антагонистами nmda и антагонистами d2/5-ht2a или селективными антагонистами 5-нт2a |
EP3675827A1 (en) | 2017-08-30 | 2020-07-08 | Acadia Pharmaceuticals Inc. | Formulations of pimavanserin |
CA3082834A1 (en) | 2017-11-22 | 2019-05-31 | Concert Pharmaceuticals, Inc. | Deuterated analogs of d-serine and uses thereof |
CN114805139B (zh) * | 2018-01-10 | 2023-10-20 | 凯瑞康宁生物工程(武汉)有限公司 | 氯胺酮的前药、其组合物和用途 |
US20220087970A1 (en) * | 2019-01-18 | 2022-03-24 | The Johns Hopkins University | Prevention of anesthetic-induced neurocognitive dysfunction |
JP2023502966A (ja) * | 2019-11-18 | 2023-01-26 | ソシエテ・デ・プロデュイ・ネスレ・エス・アー | 脳の健康に使用するためのグルタチオンの増強のための組成物及び方法 |
WO2023018966A1 (en) | 2021-08-13 | 2023-02-16 | XWPharma Ltd. | Pharmaceutical compositions and oral dosage forms of ketamine derivatives |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0283317A (ja) * | 1988-09-16 | 1990-03-23 | Takeda Chem Ind Ltd | 精神分裂病治療剤 |
WO1993010228A1 (en) * | 1991-11-12 | 1993-05-27 | Synaptic Pharmaceutical Corporation | Dna encoding a glycine transporter and uses thereof |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4904681A (en) * | 1987-12-01 | 1990-02-27 | G. D. Searle & Co. | D-cycloserine and its prodrugs as cognitive enhancers |
JP2757960B2 (ja) * | 1988-10-17 | 1998-05-25 | サントリー株式会社 | (2R,3S,4S)−α−(カルボキシシクロプロピル)グリシン |
US5187171A (en) * | 1989-01-09 | 1993-02-16 | G. D. Searle & Co. | Use of a glycine b partial agonist as an antipsychotic |
US5179085A (en) * | 1989-03-15 | 1993-01-12 | Warner-Lambert Company | N-substituted α-amino acids and derivatives thereof having pharmaceutical activity |
JPH03236315A (ja) * | 1989-12-05 | 1991-10-22 | Nippon Oil & Fats Co Ltd | 抗精神病薬 |
US5260324A (en) * | 1990-02-06 | 1993-11-09 | G. D. Searle & Company | Composition containing D-cycloserine and D-alanine for memory and learning enhancement or treatment of a cognitive or psychotic disorder |
US5086072A (en) * | 1990-06-18 | 1992-02-04 | The United States Of America As Represented By The Department Of Health And Human Services | Treatment of mood disorders with functional antagonists of the glycine/nmda receptor complex |
US5428069A (en) * | 1993-01-11 | 1995-06-27 | The United States Of America As Represented By The Department Of Health & Human Services | Treating cognition with, aminocyclopropanecarboxylic derivatives |
US5656608B1 (en) * | 1995-02-23 | 2000-09-26 | Novartis Nutrition Ltd | Amino acid compositions and methods of treatment using same |
WO1997020553A1 (en) * | 1995-12-07 | 1997-06-12 | Javitt Daniel C | Treatment of negative and cognitive symptoms of schizophrenia with glycine uptake antagonists |
-
1996
- 1996-12-05 WO PCT/US1996/019142 patent/WO1997020553A1/en active IP Right Grant
- 1996-12-05 JP JP09521348A patent/JP2000501707A/ja active Pending
- 1996-12-05 PT PT96941518T patent/PT871440E/pt unknown
- 1996-12-05 DE DE69635959T patent/DE69635959T2/de not_active Expired - Lifetime
- 1996-12-05 AT AT96941518T patent/ATE320804T1/de active
- 1996-12-05 IL IL12453696A patent/IL124536A/xx not_active IP Right Cessation
- 1996-12-05 WO PCT/US1996/019141 patent/WO1997020552A1/en active Application Filing
- 1996-12-05 DK DK96941518T patent/DK0871440T3/da active
- 1996-12-05 ES ES96941518T patent/ES2260773T3/es not_active Expired - Lifetime
- 1996-12-05 EP EP96941518A patent/EP0871440B1/en not_active Revoked
- 1996-12-06 US US08/759,681 patent/US5837730A/en not_active Expired - Lifetime
- 1996-12-06 US US08/759,714 patent/US5854286A/en not_active Expired - Lifetime
-
1998
- 1998-12-16 US US09/212,273 patent/US6162827A/en not_active Expired - Lifetime
-
2009
- 2009-03-18 JP JP2009066534A patent/JP5363152B2/ja not_active Expired - Fee Related
-
2012
- 2012-11-15 JP JP2012251233A patent/JP2013056918A/ja active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0283317A (ja) * | 1988-09-16 | 1990-03-23 | Takeda Chem Ind Ltd | 精神分裂病治療剤 |
WO1993010228A1 (en) * | 1991-11-12 | 1993-05-27 | Synaptic Pharmaceutical Corporation | Dna encoding a glycine transporter and uses thereof |
Non-Patent Citations (7)
Title |
---|
JPN6011031655; Daniel C. Javitt, et al.: Am. J. Psychiatry 148, 1991, pp.1301-1308 * |
JPN6011031656; TOSHITAKA NABESHIMA, et al.: European Journal of Pharmacology 91, 1983, pp.455-462 * |
JPN6011031657; L. J. Bristow, et al.: Br. J. Pharmacol. 108, 1993, pp.1156-1163 * |
JPN6011031659; RAUL ALLAN KIIVET, et al.: Br. J. Clin. Pharmacol. 40, 1995, pp.467-476 * |
JPN6011031660; 松野敏行ら: 九州神経精神医学 40(1), 1994, pp.117-128 * |
JPN6011031661; Francisco Zafra, et al.: The Journal of Neuroscience 15(5), 1995, pp.3952-3969 * |
JPN7011002210; Eugene Toth, et al.: Research Communications in Psychology, Psychiatry and Behavior 11(1), 1986, pp.1-9 * |
Also Published As
Publication number | Publication date |
---|---|
DE69635959T2 (de) | 2006-12-07 |
JP5363152B2 (ja) | 2013-12-11 |
EP0871440B1 (en) | 2006-03-22 |
IL124536A (en) | 2001-03-19 |
DK0871440T3 (da) | 2006-07-10 |
US5837730A (en) | 1998-11-17 |
WO1997020553A1 (en) | 1997-06-12 |
ES2260773T3 (es) | 2006-11-01 |
PT871440E (pt) | 2006-07-31 |
DE69635959D1 (de) | 2006-05-11 |
IL124536A0 (en) | 1998-12-06 |
JP2000501707A (ja) | 2000-02-15 |
EP0871440A1 (en) | 1998-10-21 |
JP2013056918A (ja) | 2013-03-28 |
US6162827A (en) | 2000-12-19 |
ATE320804T1 (de) | 2006-04-15 |
WO1997020552A1 (en) | 1997-06-12 |
EP0871440A4 (en) | 1999-01-20 |
US5854286A (en) | 1998-12-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5363152B2 (ja) | グリシン捕捉性アンタゴニストを用いる拒絶性および認知性精神分裂病症候群の処置 | |
CA3079259A1 (en) | Ganaxolone for use in treating genetic epileptic disorders | |
JP2018162321A (ja) | X連鎖副腎白質ジストロフィーの処置におけるソベチロムの使用 | |
JP5900988B2 (ja) | 抗痙攣医薬組成物 | |
Natesan et al. | Amisulpride the ‘atypical’atypical antipsychotic—comparison to haloperidol, risperidone and clozapine | |
WO2014037416A2 (en) | New therapeutic approaches for treating parkinson's disease | |
US20100016207A1 (en) | Methods and Compositions for Raising Levels and Release of Gamma Aminobutyric Acid | |
JP2000514420A (ja) | 末梢または中枢神経障害およびサイトカイン過剰産生の治療のためのk―252a誘導体の使用 | |
JP2019023195A (ja) | L−4−クロロキヌレニンの剤形及び治療的使用 | |
JP2001520994A (ja) | 消化管疾患を治療するためにクマリン誘導体を用いる用途 | |
US20110288145A1 (en) | Novel Formulation For L-Tryptophane Comprising Carbidopa/Benserazide | |
CN114007607A (zh) | 用于治疗神经变性疾病的材料和方法 | |
Rainsford et al. | Recent pharmacodynamic and pharmacokinetic findings on oxaprozin | |
Ferreira et al. | Ionotropic glutamate receptor subunit expression in the rat hippocampus: lack of an effect of a long‐term ethanol exposure paradigm | |
Magnussen et al. | Treatment of myoclonic syndromes with paroxetine alone or combined with 5‐HTP | |
Brodnik et al. | Presynaptic regulation of extracellular dopamine levels in the medial prefrontal cortex and striatum during tyrosine depletion | |
JP2017533967A (ja) | システアミン組成物を用いるハンチントン病の処置方法 | |
EP1383496A2 (en) | Treatment of fibromyalgia and related fatigue syndromes using pindolol | |
EP1830833B1 (en) | Combination of a glycine transporter (glyt1) inhibitor and an antipsychotic for the treatment of symptoms of schizophrenia as well as its preparation and use thereof | |
JP6227535B2 (ja) | 脂質異常症の予防又は治療薬 | |
JPH0276813A (ja) | 神経変性疾患の治療薬 | |
CA2239624C (en) | Treatment of negative and cognitive symptoms of schizophrenia with glycine uptake antagonists | |
US20110172171A1 (en) | Taurine or taurine-like substances for the prevention of brain oedema | |
JP7257091B2 (ja) | 認知症の治療及び予防薬 | |
JP2002220345A (ja) | 脂肪肝改善剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20090515 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20090518 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20090907 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20090907 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120515 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120813 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120816 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120910 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120913 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20121011 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20121016 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121115 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130212 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130611 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20130731 |
|
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: 20130820 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130905 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |