ES2974824T3 - Potenciadores del receptor de AMPA - Google Patents

Info

Publication number

ES2974824T3

ES2974824T3 ES18705480T ES18705480T ES2974824T3 ES 2974824 T3 ES2974824 T3 ES 2974824T3 ES 18705480 T ES18705480 T ES 18705480T ES 18705480 T ES18705480 T ES 18705480T ES 2974824 T3 ES2974824 T3 ES 2974824T3

Authority

ES

Spain

Prior art keywords

compound

disorder

alkyl

treatment

disorders

Prior art date

2017-02-10

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 102000003678 AMPA Receptors Human genes 0.000 title claims abstract description 76
• 108090000078 AMPA Receptors Proteins 0.000 title claims abstract description 76
• 239000003623 enhancer Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 259
• 238000011282 treatment Methods 0.000 claims abstract description 95
• 239000003814 drug Substances 0.000 claims abstract description 60
• 208000020401 Depressive disease Diseases 0.000 claims abstract description 58
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 52
• 208000010877 cognitive disease Diseases 0.000 claims abstract description 36
• 201000000980 schizophrenia Diseases 0.000 claims abstract description 28
• 208000019022 Mood disease Diseases 0.000 claims abstract description 24
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
• 208000015114 central nervous system disease Diseases 0.000 claims abstract description 5
• 125000000217 alkyl group Chemical group 0.000 claims description 32
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
• 208000035475 disorder Diseases 0.000 claims description 31
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 30
• 229940124597 therapeutic agent Drugs 0.000 claims description 30
• 230000003956 synaptic plasticity Effects 0.000 claims description 17
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
• 239000000935 antidepressant agent Substances 0.000 claims description 15
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 15
• 208000020925 Bipolar disease Diseases 0.000 claims description 14
• 230000001430 anti-depressive effect Effects 0.000 claims description 14
• 229940005513 antidepressants Drugs 0.000 claims description 14
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 13
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 13
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
• 208000024827 Alzheimer disease Diseases 0.000 claims description 10
• 208000004756 Respiratory Insufficiency Diseases 0.000 claims description 10
• 206010038678 Respiratory depression Diseases 0.000 claims description 10
• 230000003920 cognitive function Effects 0.000 claims description 10
• 230000000926 neurological effect Effects 0.000 claims description 10
• 208000018737 Parkinson disease Diseases 0.000 claims description 9
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
• 208000023105 Huntington disease Diseases 0.000 claims description 8
• 208000028552 Treatment-Resistant Depressive disease Diseases 0.000 claims description 8
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 8
• 230000009540 excitatory neurotransmission Effects 0.000 claims description 7
• 230000009539 inhibitory neurotransmission Effects 0.000 claims description 7
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 5
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 5
• 208000012902 Nervous system disease Diseases 0.000 claims description 5
• 230000004075 alteration Effects 0.000 claims description 5
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 5
• 206010003591 Ataxia Diseases 0.000 claims description 3
• 208000016621 Hearing disease Diseases 0.000 claims description 3
• 208000026072 Motor neurone disease Diseases 0.000 claims description 3
• 208000029726 Neurodevelopmental disease Diseases 0.000 claims description 3
• 230000000561 anti-psychotic effect Effects 0.000 claims description 3
• 208000005264 motor neuron disease Diseases 0.000 claims description 3
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 6
• 241000117281 Aora Species 0.000 claims 1
• 230000003389 potentiating effect Effects 0.000 abstract description 11
• XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 103
• 235000019439 ethyl acetate Nutrition 0.000 description 51
• 238000000034 method Methods 0.000 description 45
• 230000000694 effects Effects 0.000 description 40
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 38
• 208000024891 symptom Diseases 0.000 description 38
• 208000019901 Anxiety disease Diseases 0.000 description 34
• 239000003208 petroleum Substances 0.000 description 34
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 28
• -1 7-phenoxy-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides Chemical class 0.000 description 26
• 239000000047 product Substances 0.000 description 26
• 239000003153 chemical reaction reagent Substances 0.000 description 24
• 238000004440 column chromatography Methods 0.000 description 24
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 23
• FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 22
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
• 239000012043 crude product Substances 0.000 description 22
• 208000024714 major depressive disease Diseases 0.000 description 22
• 229940079593 drug Drugs 0.000 description 21
• 239000000741 silica gel Substances 0.000 description 21
• 229910002027 silica gel Inorganic materials 0.000 description 21
• 238000005160 1H NMR spectroscopy Methods 0.000 description 20
• 201000010099 disease Diseases 0.000 description 20
• 239000007787 solid Substances 0.000 description 20
• BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 18
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
• RTARXVOVNNZAGO-UHFFFAOYSA-N 1-[(4-iodophenyl)methyl]pyrrolidin-2-one Chemical compound C1=CC(I)=CC=C1CN1C(=O)CCC1 RTARXVOVNNZAGO-UHFFFAOYSA-N 0.000 description 16
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 16
• 230000036506 anxiety Effects 0.000 description 16
• 238000006243 chemical reaction Methods 0.000 description 16
• 229930195712 glutamate Natural products 0.000 description 16
• 229940049906 glutamate Drugs 0.000 description 16
• 239000000203 mixture Substances 0.000 description 16
• 102000005962 receptors Human genes 0.000 description 16
• 108020003175 receptors Proteins 0.000 description 16
• 208000028017 Psychotic disease Diseases 0.000 description 15
• 239000011541 reaction mixture Substances 0.000 description 15
• 208000028698 Cognitive impairment Diseases 0.000 description 14
• YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 14
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
• 238000012360 testing method Methods 0.000 description 14
• 150000003839 salts Chemical class 0.000 description 13
• 230000001225 therapeutic effect Effects 0.000 description 13
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 12
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 12
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 12
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 12
• 210000004556 brain Anatomy 0.000 description 11
• 229910000024 caesium carbonate Inorganic materials 0.000 description 11
• 229910052799 carbon Inorganic materials 0.000 description 11
• 210000003169 central nervous system Anatomy 0.000 description 11
• 108700003601 dimethylglycine Proteins 0.000 description 11
• 229960003299 ketamine Drugs 0.000 description 11
• 229940078490 n,n-dimethylglycine Drugs 0.000 description 11
• 230000002829 reductive effect Effects 0.000 description 11
• UUDAMDVQRQNNHZ-UHFFFAOYSA-N (S)-AMPA Chemical compound CC=1ONC(=O)C=1CC(N)C(O)=O UUDAMDVQRQNNHZ-UHFFFAOYSA-N 0.000 description 10
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
• 206010042458 Suicidal ideation Diseases 0.000 description 10
• 230000003001 depressive effect Effects 0.000 description 10
• 230000006870 function Effects 0.000 description 10
• 230000001965 increasing effect Effects 0.000 description 10
• 241000700159 Rattus Species 0.000 description 9
• 230000003281 allosteric effect Effects 0.000 description 9
• 230000009286 beneficial effect Effects 0.000 description 9
• 239000010410 layer Substances 0.000 description 9
• 230000002085 persistent effect Effects 0.000 description 9
• 229940126027 positive allosteric modulator Drugs 0.000 description 9
• 239000000243 solution Substances 0.000 description 9
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
• 208000002193 Pain Diseases 0.000 description 8
• 238000003556 assay Methods 0.000 description 8
• 239000012267 brine Substances 0.000 description 8
• 239000012280 lithium aluminium hydride Substances 0.000 description 8
• 239000003921 oil Substances 0.000 description 8
• 230000009467 reduction Effects 0.000 description 8
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
• 238000003786 synthesis reaction Methods 0.000 description 8
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
• 108091006146 Channels Proteins 0.000 description 7
• 206010012289 Dementia Diseases 0.000 description 7
• 102000004310 Ion Channels Human genes 0.000 description 7
• 108090000862 Ion Channels Proteins 0.000 description 7
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
• HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 7
• 208000028683 bipolar I disease Diseases 0.000 description 7
• 210000004027 cell Anatomy 0.000 description 7
• 230000019771 cognition Effects 0.000 description 7
• 208000014674 injury Diseases 0.000 description 7
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
• 235000019341 magnesium sulphate Nutrition 0.000 description 7
• 230000015654 memory Effects 0.000 description 7
• 230000000216 proconvulsive effect Effects 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 206010026749 Mania Diseases 0.000 description 6
• 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 6
• 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 6
• 208000027418 Wounds and injury Diseases 0.000 description 6
• 239000000556 agonist Substances 0.000 description 6
• 230000006378 damage Effects 0.000 description 6
• 208000024732 dysthymic disease Diseases 0.000 description 6
• 230000002708 enhancing effect Effects 0.000 description 6
• 230000000848 glutamatergic effect Effects 0.000 description 6
• 108020001756 ligand binding domains Proteins 0.000 description 6
• 229910001629 magnesium chloride Inorganic materials 0.000 description 6
• 239000012044 organic layer Substances 0.000 description 6
• 230000002265 prevention Effects 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• 239000003775 serotonin noradrenalin reuptake inhibitor Substances 0.000 description 6
• 230000035882 stress Effects 0.000 description 6
• 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 5
• BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 5
• 206010010904 Convulsion Diseases 0.000 description 5
• 102000018899 Glutamate Receptors Human genes 0.000 description 5
• 108010027915 Glutamate Receptors Proteins 0.000 description 5
• 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 5
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 5
• 241000283984 Rodentia Species 0.000 description 5
• 208000006011 Stroke Diseases 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 229910001424 calcium ion Inorganic materials 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 239000002552 dosage form Substances 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 230000013016 learning Effects 0.000 description 5
• 230000027928 long-term synaptic potentiation Effects 0.000 description 5
• 239000002899 monoamine oxidase inhibitor Substances 0.000 description 5
• 208000019906 panic disease Diseases 0.000 description 5
• 230000007170 pathology Effects 0.000 description 5
• 239000008188 pellet Substances 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 230000003414 procognitive effect Effects 0.000 description 5
• 230000000069 prophylactic effect Effects 0.000 description 5
• 208000020016 psychiatric disease Diseases 0.000 description 5
• 230000004044 response Effects 0.000 description 5
• 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 5
• 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• 239000000758 substrate Substances 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• LWQHMUKTJLEHFL-UHFFFAOYSA-N 1-[[4-[5-(hydroxymethyl)-4-methyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]methyl]pyrrolidin-2-one Chemical compound OCC1=C(C(=NN1C1=CC=C(C=C1)CN1C(CCC1)=O)C(F)(F)F)C LWQHMUKTJLEHFL-UHFFFAOYSA-N 0.000 description 4
• PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• 102100030651 Glutamate receptor 2 Human genes 0.000 description 4
• 101710087631 Glutamate receptor 2 Proteins 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• 101001017818 Homo sapiens ATP-dependent translocase ABCB1 Proteins 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• 229940121991 Serotonin and norepinephrine reuptake inhibitor Drugs 0.000 description 4
• 206010041250 Social phobia Diseases 0.000 description 4
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
• 229940123445 Tricyclic antidepressant Drugs 0.000 description 4
• WJQGPRJXZGEUSV-UHFFFAOYSA-N [4-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]methanol Chemical compound CC=1C(=NNC=1CO)C(F)(F)F WJQGPRJXZGEUSV-UHFFFAOYSA-N 0.000 description 4
• 239000013543 active substance Substances 0.000 description 4
• 230000001154 acute effect Effects 0.000 description 4
• 239000002249 anxiolytic agent Substances 0.000 description 4
• 238000013459 approach Methods 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 238000007796 conventional method Methods 0.000 description 4
• 230000002920 convulsive effect Effects 0.000 description 4
• ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 4
• ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 4
• 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 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 230000006872 improvement Effects 0.000 description 4
• 230000006698 induction Effects 0.000 description 4
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
• 230000004770 neurodegeneration Effects 0.000 description 4
• 230000000144 pharmacologic effect Effects 0.000 description 4
• 229920002401 polyacrylamide Polymers 0.000 description 4
• 238000002360 preparation method Methods 0.000 description 4
• 229940002612 prodrug Drugs 0.000 description 4
• 239000000651 prodrug Substances 0.000 description 4
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 4
• 230000000306 recurrent effect Effects 0.000 description 4
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
• 239000012453 solvate Substances 0.000 description 4
• 239000003029 tricyclic antidepressant agent Substances 0.000 description 4
• 229960000607 ziprasidone Drugs 0.000 description 4
• MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 4
• SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 3
• 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 3
• 208000031091 Amnestic disease Diseases 0.000 description 3
• 206010002869 Anxiety symptoms Diseases 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• 208000000094 Chronic Pain Diseases 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
• 241000699666 Mus <mouse, genus> Species 0.000 description 3
• 238000005481 NMR spectroscopy Methods 0.000 description 3
• 208000026251 Opioid-Related disease Diseases 0.000 description 3
• 206010034912 Phobia Diseases 0.000 description 3
• 238000010357 RNA editing Methods 0.000 description 3
• 230000026279 RNA modification Effects 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 230000032683 aging Effects 0.000 description 3
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 3
• 239000000164 antipsychotic agent Substances 0.000 description 3
• 230000003542 behavioural effect Effects 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• 229940049706 benzodiazepine Drugs 0.000 description 3
• 150000001557 benzodiazepines Chemical class 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 229910052794 bromium Inorganic materials 0.000 description 3
• 206010007776 catatonia Diseases 0.000 description 3
• 239000000460 chlorine Substances 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• 230000001684 chronic effect Effects 0.000 description 3
• 239000013078 crystal Substances 0.000 description 3
• 239000000539 dimer Substances 0.000 description 3
• 230000009977 dual effect Effects 0.000 description 3
• 238000002635 electroconvulsive therapy Methods 0.000 description 3
• LFSVADABIDBSBV-UHFFFAOYSA-N ethyl 3-cyclopropyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C1CC1 LFSVADABIDBSBV-UHFFFAOYSA-N 0.000 description 3
• NHPQFPJBSQYSNZ-UHFFFAOYSA-N ethyl 5-cyclopropyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate Chemical compound CCOC(=O)C1=C(NN=C1C1CC1)C(F)(F)F NHPQFPJBSQYSNZ-UHFFFAOYSA-N 0.000 description 3
• 206010016256 fatigue Diseases 0.000 description 3
• 230000002349 favourable effect Effects 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 229910052739 hydrogen Inorganic materials 0.000 description 3
• 230000001771 impaired effect Effects 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 230000004941 influx Effects 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 150000002500 ions Chemical class 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
• GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 3
• 210000001589 microsome Anatomy 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
• 238000011457 non-pharmacological treatment Methods 0.000 description 3
• 229960002748 norepinephrine Drugs 0.000 description 3
• SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 3
• 230000035515 penetration Effects 0.000 description 3
• 229940124531 pharmaceutical excipient Drugs 0.000 description 3
• 208000028173 post-traumatic stress disease Diseases 0.000 description 3
• 239000002243 precursor Substances 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 208000012672 seasonal affective disease Diseases 0.000 description 3
• 208000011117 substance-related disease Diseases 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 230000000946 synaptic effect Effects 0.000 description 3
• 230000005062 synaptic transmission Effects 0.000 description 3
• 239000003174 triple reuptake inhibitor Substances 0.000 description 3
• GJJFMKBJSRMPLA-HIFRSBDPSA-N (1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenyl-1-cyclopropanecarboxamide Chemical compound C=1C=CC=CC=1[C@@]1(C(=O)N(CC)CC)C[C@@H]1CN GJJFMKBJSRMPLA-HIFRSBDPSA-N 0.000 description 2
• DIWRORZWFLOCLC-HNNXBMFYSA-N (3s)-7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N([C@H](C(NC1=CC=C(Cl)C=C11)=O)O)=C1C1=CC=CC=C1Cl DIWRORZWFLOCLC-HNNXBMFYSA-N 0.000 description 2
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
• YQEZLKZALYSWHR-ZDUSSCGKSA-N (S)-ketamine Chemical compound C=1C=CC=C(Cl)C=1[C@@]1(NC)CCCCC1=O YQEZLKZALYSWHR-ZDUSSCGKSA-N 0.000 description 2
• NFURBQRLBWRXLR-UHFFFAOYSA-N 1-[4-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]ethanol Chemical compound CC=1C(=NNC=1C(C)O)C(F)(F)F NFURBQRLBWRXLR-UHFFFAOYSA-N 0.000 description 2
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• PMXMIIMHBWHSKN-UHFFFAOYSA-N 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCC(O)C4=NC=3C)=NOC2=C1 PMXMIIMHBWHSKN-UHFFFAOYSA-N 0.000 description 2
• XCMQUYJMNQEMMK-UHFFFAOYSA-N 4-methyl-5-(trifluoromethyl)-1h-pyrazole-3-carbaldehyde Chemical compound CC=1C(C=O)=NNC=1C(F)(F)F XCMQUYJMNQEMMK-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
• 239000005695 Ammonium acetate Substances 0.000 description 2
• 208000007415 Anhedonia Diseases 0.000 description 2
• CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 2
• 206010003805 Autism Diseases 0.000 description 2
• 208000020706 Autistic disease Diseases 0.000 description 2
• CYGODHVAJQTCBG-UHFFFAOYSA-N Bifeprunox Chemical compound C=12OC(=O)NC2=CC=CC=1N(CC1)CCN1CC(C=1)=CC=CC=1C1=CC=CC=C1 CYGODHVAJQTCBG-UHFFFAOYSA-N 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 208000003417 Central Sleep Apnea Diseases 0.000 description 2
• QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 2
• 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 description 2
• 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 2
• 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 2
• 206010011878 Deafness Diseases 0.000 description 2
• 206010011971 Decreased interest Diseases 0.000 description 2
• 206010012218 Delirium Diseases 0.000 description 2
• 206010012335 Dependence Diseases 0.000 description 2
• 201000010374 Down Syndrome Diseases 0.000 description 2
• 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 2
• UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
• 208000011688 Generalised anxiety disease Diseases 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• 239000012981 Hank's balanced salt solution Substances 0.000 description 2
• 206010020710 Hyperphagia Diseases 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• VLSMHEGGTFMBBZ-OOZYFLPDSA-M Kainate Chemical compound CC(=C)[C@H]1C[NH2+][C@H](C([O-])=O)[C@H]1CC([O-])=O VLSMHEGGTFMBBZ-OOZYFLPDSA-M 0.000 description 2
• 229910010084 LiAlH4 Inorganic materials 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 2
• 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 description 2
• KLPWJLBORRMFGK-UHFFFAOYSA-N Molindone Chemical compound O=C1C=2C(CC)=C(C)NC=2CCC1CN1CCOCC1 KLPWJLBORRMFGK-UHFFFAOYSA-N 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 2
• 208000008589 Obesity Diseases 0.000 description 2
• 206010033664 Panic attack Diseases 0.000 description 2
• 208000027099 Paranoid disease Diseases 0.000 description 2
• RGCVKNLCSQQDEP-UHFFFAOYSA-N Perphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 RGCVKNLCSQQDEP-UHFFFAOYSA-N 0.000 description 2
• 201000009916 Postpartum depression Diseases 0.000 description 2
• 208000027030 Premenstrual dysphoric disease Diseases 0.000 description 2
• 208000006289 Rett Syndrome Diseases 0.000 description 2
• 201000001880 Sexual dysfunction Diseases 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• 208000011963 Substance-induced psychotic disease Diseases 0.000 description 2
• 231100000393 Substance-induced psychotic disorder Toxicity 0.000 description 2
• 206010043118 Tardive Dyskinesia Diseases 0.000 description 2
• KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 description 2
• 208000009205 Tinnitus Diseases 0.000 description 2
• 208000030886 Traumatic Brain injury Diseases 0.000 description 2
• DNRBURPRAASZAL-UHFFFAOYSA-N [5-ethyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methanol Chemical compound C(C)C1=C(C(=NN1)C(F)(F)F)CO DNRBURPRAASZAL-UHFFFAOYSA-N 0.000 description 2
• NTGGDBBIWZYNDG-UHFFFAOYSA-N [5-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methanol Chemical compound CC1=C(C(=NN1)C(F)(F)F)CO NTGGDBBIWZYNDG-UHFFFAOYSA-N 0.000 description 2
• WJHMDCAWISOINA-UHFFFAOYSA-N [5-propan-2-yl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methanol Chemical compound FC(C=1C(CO)=C(C(C)C)NN=1)(F)F WJHMDCAWISOINA-UHFFFAOYSA-N 0.000 description 2
• XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
• ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 230000002411 adverse Effects 0.000 description 2
• 229960004538 alprazolam Drugs 0.000 description 2
• 229960003036 amisulpride Drugs 0.000 description 2
• NTJOBXMMWNYJFB-UHFFFAOYSA-N amisulpride Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC)=C(N)C=C1OC NTJOBXMMWNYJFB-UHFFFAOYSA-N 0.000 description 2
• 235000019257 ammonium acetate Nutrition 0.000 description 2
• 229940043376 ammonium acetate Drugs 0.000 description 2
• VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 2
• 229940025084 amphetamine Drugs 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 229940005529 antipsychotics Drugs 0.000 description 2
• 230000000949 anxiolytic effect Effects 0.000 description 2
• 229960004372 aripiprazole Drugs 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• 239000003693 atypical antipsychotic agent Substances 0.000 description 2
• 229940127236 atypical antipsychotics Drugs 0.000 description 2
• 229940125717 barbiturate Drugs 0.000 description 2
• 230000004888 barrier function Effects 0.000 description 2
• 229950009087 bifeprunox Drugs 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• 208000025307 bipolar depression Diseases 0.000 description 2
• 230000008499 blood brain barrier function Effects 0.000 description 2
• 210000001218 blood-brain barrier Anatomy 0.000 description 2
• 229960001058 bupropion Drugs 0.000 description 2
• SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 2
• ZRIHAIZYIMGOAB-UHFFFAOYSA-N butabarbital Chemical compound CCC(C)C1(CC)C(=O)NC(=O)NC1=O ZRIHAIZYIMGOAB-UHFFFAOYSA-N 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 230000008859 change Effects 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
• 239000000544 cholinesterase inhibitor Substances 0.000 description 2
• 230000007012 clinical effect Effects 0.000 description 2
• 229960004170 clozapine Drugs 0.000 description 2
• QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
• 238000011260 co-administration Methods 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
• 230000001149 cognitive effect Effects 0.000 description 2
• 239000002475 cognitive enhancer Substances 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 230000007850 degeneration Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000000586 desensitisation Methods 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 229960003530 donepezil Drugs 0.000 description 2
• 230000036267 drug metabolism Effects 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 201000003104 endogenous depression Diseases 0.000 description 2
• 230000007613 environmental effect Effects 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• 229960000450 esketamine Drugs 0.000 description 2
• UDRCONFHWYGWFI-UHFFFAOYSA-N ethyl 3-oxopentanoate Chemical compound CCOC(=O)CC(=O)CC UDRCONFHWYGWFI-UHFFFAOYSA-N 0.000 description 2
• XCLDSQRVMMXWMS-UHFFFAOYSA-N ethyl 4-methyl-3-oxopentanoate Chemical compound CCOC(=O)CC(=O)C(C)C XCLDSQRVMMXWMS-UHFFFAOYSA-N 0.000 description 2
• IJAILHSJRXFPQC-UHFFFAOYSA-N ethyl 5-ethyl-3-(trifluoromethyl)-1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C1=C(CC)NN=C1C(F)(F)F IJAILHSJRXFPQC-UHFFFAOYSA-N 0.000 description 2
• NWWMRPQFYNSAQH-UHFFFAOYSA-N ethyl 5-methyl-3-(trifluoromethyl)-1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C1=C(C)NN=C1C(F)(F)F NWWMRPQFYNSAQH-UHFFFAOYSA-N 0.000 description 2
• MZPNPLMBFBCAJG-UHFFFAOYSA-N ethyl 5-propan-2-yl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate Chemical compound CCOC(=O)C1=C(C(C)C)NN=C1C(F)(F)F MZPNPLMBFBCAJG-UHFFFAOYSA-N 0.000 description 2
• XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
• 238000011156 evaluation Methods 0.000 description 2
• 229960002690 fluphenazine Drugs 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 229960003980 galantamine Drugs 0.000 description 2
• ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 2
• 208000029364 generalized anxiety disease Diseases 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 229960003878 haloperidol Drugs 0.000 description 2
• 230000010370 hearing loss Effects 0.000 description 2
• 231100000888 hearing loss Toxicity 0.000 description 2
• 208000016354 hearing loss disease Diseases 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• ZTUJDPKOHPKRMO-UHFFFAOYSA-N hydron;2,2,2-trifluoroethanamine;chloride Chemical compound Cl.NCC(F)(F)F ZTUJDPKOHPKRMO-UHFFFAOYSA-N 0.000 description 2
• 206010022437 insomnia Diseases 0.000 description 2
• 239000000543 intermediate Substances 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000007912 intraperitoneal administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 229960001078 lithium Drugs 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• 229960004391 lorazepam Drugs 0.000 description 2
• 229960000423 loxapine Drugs 0.000 description 2
• XJGVXQDUIWGIRW-UHFFFAOYSA-N loxapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2OC2=CC=C(Cl)C=C12 XJGVXQDUIWGIRW-UHFFFAOYSA-N 0.000 description 2
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 230000028161 membrane depolarization Effects 0.000 description 2
• 229960000300 mesoridazine Drugs 0.000 description 2
• SLVMESMUVMCQIY-UHFFFAOYSA-N mesoridazine Chemical compound CN1CCCCC1CCN1C2=CC(S(C)=O)=CC=C2SC2=CC=CC=C21 SLVMESMUVMCQIY-UHFFFAOYSA-N 0.000 description 2
• 230000002503 metabolic effect Effects 0.000 description 2
• 239000002207 metabolite Substances 0.000 description 2
• 108010038421 metabotropic glutamate receptor 2 Proteins 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• MCVVUJPXSBQTRZ-ONEGZZNKSA-N methyl (e)-but-2-enoate Chemical compound COC(=O)\C=C\C MCVVUJPXSBQTRZ-ONEGZZNKSA-N 0.000 description 2
• WOSFUGOCUQPOMA-UHFFFAOYSA-N methyl 4-methyl-5-(trifluoromethyl)-1h-pyrazole-3-carboxylate Chemical compound COC(=O)C1=NNC(C(F)(F)F)=C1C WOSFUGOCUQPOMA-UHFFFAOYSA-N 0.000 description 2
• OPLSAQOMIUQCJI-UHFFFAOYSA-N methyl 4-methyl-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-3-carboxylate Chemical compound CC1C(=NNC1C(F)(F)F)C(=O)OC OPLSAQOMIUQCJI-UHFFFAOYSA-N 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 229960004938 molindone Drugs 0.000 description 2
• 230000036651 mood Effects 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• 229960001800 nefazodone Drugs 0.000 description 2
• VRBKIVRKKCLPHA-UHFFFAOYSA-N nefazodone Chemical compound O=C1N(CCOC=2C=CC=CC=2)C(CC)=NN1CCCN(CC1)CCN1C1=CC=CC(Cl)=C1 VRBKIVRKKCLPHA-UHFFFAOYSA-N 0.000 description 2
• 230000007383 nerve stimulation Effects 0.000 description 2
• 230000001537 neural effect Effects 0.000 description 2
• 210000002569 neuron Anatomy 0.000 description 2
• 230000000324 neuroprotective effect Effects 0.000 description 2
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• 229960001158 nortriptyline Drugs 0.000 description 2
• 235000020824 obesity Nutrition 0.000 description 2
• 229960005017 olanzapine Drugs 0.000 description 2
• KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 2
• 235000020830 overeating Nutrition 0.000 description 2
• 229960001057 paliperidone Drugs 0.000 description 2
• WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
• 229960000762 perphenazine Drugs 0.000 description 2
• 238000011458 pharmacological treatment Methods 0.000 description 2
• DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 2
• 230000000704 physical effect Effects 0.000 description 2
• 239000011148 porous material Substances 0.000 description 2
• 238000012877 positron emission topography Methods 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 239000012286 potassium permanganate Substances 0.000 description 2
• 229960003111 prochlorperazine Drugs 0.000 description 2
• WIKYUJGCLQQFNW-UHFFFAOYSA-N prochlorperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 WIKYUJGCLQQFNW-UHFFFAOYSA-N 0.000 description 2
• 230000001737 promoting effect Effects 0.000 description 2
• 238000001671 psychotherapy Methods 0.000 description 2
• 229960004431 quetiapine Drugs 0.000 description 2
• URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 2
• 230000002285 radioactive effect Effects 0.000 description 2
• 239000000018 receptor agonist Substances 0.000 description 2
• 229940044601 receptor agonist Drugs 0.000 description 2
• 229940044551 receptor antagonist Drugs 0.000 description 2
• 239000002464 receptor antagonist Substances 0.000 description 2
• 229940075993 receptor modulator Drugs 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 229960001534 risperidone Drugs 0.000 description 2
• 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 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 229940076279 serotonin Drugs 0.000 description 2
• 239000003772 serotonin uptake inhibitor Substances 0.000 description 2
• 208000019116 sleep disease Diseases 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 235000010288 sodium nitrite Nutrition 0.000 description 2
• 201000001716 specific phobia Diseases 0.000 description 2
• 208000020431 spinal cord injury Diseases 0.000 description 2
• 230000003019 stabilising effect Effects 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 210000000225 synapse Anatomy 0.000 description 2
• 230000024587 synaptic transmission, glutamatergic Effects 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• 230000002123 temporal effect Effects 0.000 description 2
• 229960002784 thioridazine Drugs 0.000 description 2
• 231100000886 tinnitus Toxicity 0.000 description 2
• 238000011491 transcranial magnetic stimulation Methods 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 230000009529 traumatic brain injury Effects 0.000 description 2
• 229960003991 trazodone Drugs 0.000 description 2
• PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 description 2
• 229960002324 trifluoperazine Drugs 0.000 description 2
• ZEWQUBUPAILYHI-UHFFFAOYSA-N trifluoperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 ZEWQUBUPAILYHI-UHFFFAOYSA-N 0.000 description 2
• 229960002431 trimipramine Drugs 0.000 description 2
• ZSCDBOWYZJWBIY-UHFFFAOYSA-N trimipramine Chemical compound C1CC2=CC=CC=C2N(CC(CN(C)C)C)C2=CC=CC=C21 ZSCDBOWYZJWBIY-UHFFFAOYSA-N 0.000 description 2
• 210000001186 vagus nerve Anatomy 0.000 description 2
• MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 2
• 229960000604 valproic acid Drugs 0.000 description 2
• 229960004688 venlafaxine Drugs 0.000 description 2
• PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 2
• 230000001755 vocal effect Effects 0.000 description 2
• 239000003643 water by type Substances 0.000 description 2
• AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 1
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
• IGLYMJRIWWIQQE-QUOODJBBSA-N (1S,2R)-2-phenylcyclopropan-1-amine (1R,2S)-2-phenylcyclopropan-1-amine Chemical compound N[C@H]1C[C@@H]1C1=CC=CC=C1.N[C@@H]1C[C@H]1C1=CC=CC=C1 IGLYMJRIWWIQQE-QUOODJBBSA-N 0.000 description 1
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
• VOYCNOJFAJAILW-CAMHOICYSA-N (1r,4s,5s,6s)-4-[[(2s)-2-amino-4-methylsulfanylbutanoyl]amino]-2,2-dioxo-2$l^{6}-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@]1(C(O)=O)CS(=O)(=O)[C@H]2[C@H](C(O)=O)[C@@H]12 VOYCNOJFAJAILW-CAMHOICYSA-N 0.000 description 1
• WYDUSKDSKCASEF-LJQANCHMSA-N (1s)-1-cyclohexyl-1-phenyl-3-pyrrolidin-1-ylpropan-1-ol Chemical compound C([C@](O)(C1CCCCC1)C=1C=CC=CC=1)CN1CCCC1 WYDUSKDSKCASEF-LJQANCHMSA-N 0.000 description 1
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
• YWPHCCPCQOJSGZ-LLVKDONJSA-N (2r)-2-[(2-ethoxyphenoxy)methyl]morpholine Chemical compound CCOC1=CC=CC=C1OC[C@@H]1OCCNC1 YWPHCCPCQOJSGZ-LLVKDONJSA-N 0.000 description 1
• CFBVGSWSOJBYGC-ZYHUDNBSSA-N (2r,6r)-2-amino-2-(2-chlorophenyl)-6-hydroxycyclohexan-1-one Chemical compound C=1C=CC=C(Cl)C=1[C@]1(N)CCC[C@@H](O)C1=O CFBVGSWSOJBYGC-ZYHUDNBSSA-N 0.000 description 1
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
• OMPCVMLFFSQFIX-CONSDPRKSA-N (2s,3s)-2-benzhydryl-n-[(5-tert-butyl-2-methoxyphenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine Chemical compound COC1=CC=C(C(C)(C)C)C=C1CN[C@@H]1[C@H](C(C=2C=CC=CC=2)C=2C=CC=CC=2)N2CCC1CC2 OMPCVMLFFSQFIX-CONSDPRKSA-N 0.000 description 1
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
• WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 1
• RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
• ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 1
• TZJUVVIWVWFLCD-UHFFFAOYSA-N 1,1-dioxo-2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-1,2-benzothiazol-3-one Chemical compound O=S1(=O)C2=CC=CC=C2C(=O)N1CCCCN(CC1)CCN1C1=NC=CC=N1 TZJUVVIWVWFLCD-UHFFFAOYSA-N 0.000 description 1
• KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
• POPPVIRYGJQIOF-UHFFFAOYSA-N 2-acetyloxyethyl(trimethyl)azanium;3-(1-methylpyrrolidin-2-yl)pyridine Chemical compound CC(=O)OCC[N+](C)(C)C.CN1CCCC1C1=CC=CN=C1 POPPVIRYGJQIOF-UHFFFAOYSA-N 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• BIAVGWDGIJKWRM-FQEVSTJZSA-N 3-hydroxy-2-phenyl-n-[(1s)-1-phenylpropyl]quinoline-4-carboxamide Chemical compound N([C@@H](CC)C=1C=CC=CC=1)C(=O)C(C1=CC=CC=C1N=1)=C(O)C=1C1=CC=CC=C1 BIAVGWDGIJKWRM-FQEVSTJZSA-N 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• RHPHFGSTWHGREC-UHFFFAOYSA-N 4-methyl-2-[4-[(2-oxopyrrolidin-1-yl)methyl]phenyl]-5-(trifluoromethyl)pyrazole-3-carbonitrile Chemical compound CC1=C(N(N=C1C(F)(F)F)C1=CC=C(C=C1)CN1C(CCC1)=O)C#N RHPHFGSTWHGREC-UHFFFAOYSA-N 0.000 description 1
• OPQJIUBZTPCPML-UHFFFAOYSA-N 5-ethyl-3-(trifluoromethyl)-1h-pyrazole-4-carboxylic acid Chemical compound CCC=1NN=C(C(F)(F)F)C=1C(O)=O OPQJIUBZTPCPML-UHFFFAOYSA-N 0.000 description 1
• 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 1
• 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
• XKFPYPQQHFEXRZ-UHFFFAOYSA-N 5-methyl-N'-(phenylmethyl)-3-isoxazolecarbohydrazide Chemical compound O1C(C)=CC(C(=O)NNCC=2C=CC=CC=2)=N1 XKFPYPQQHFEXRZ-UHFFFAOYSA-N 0.000 description 1
• 206010065040 AIDS dementia complex Diseases 0.000 description 1
• 206010001022 Acute psychosis Diseases 0.000 description 1
• 108060003345 Adrenergic Receptor Proteins 0.000 description 1
• 102000017910 Adrenergic receptor Human genes 0.000 description 1
• 208000017194 Affective disease Diseases 0.000 description 1
• 206010001497 Agitation Diseases 0.000 description 1
• 208000008811 Agoraphobia Diseases 0.000 description 1
• 229940124810 Alzheimer's drug Drugs 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 208000029197 Amphetamine-Related disease Diseases 0.000 description 1
• 206010002942 Apathy Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 208000036640 Asperger disease Diseases 0.000 description 1
• 201000006062 Asperger syndrome Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
• 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
• 206010006362 Brief psychotic disorder, with postpartum onset Diseases 0.000 description 1
• 208000011597 CGF1 Diseases 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 241000218236 Cannabis Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
• 206010008027 Cerebellar atrophy Diseases 0.000 description 1
• 208000007192 Childhood Schizophrenia Diseases 0.000 description 1
• 206010008748 Chorea Diseases 0.000 description 1
• GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 1
• 208000022497 Cocaine-Related disease Diseases 0.000 description 1
• 206010010144 Completed suicide Diseases 0.000 description 1
• 229940126657 Compound 17 Drugs 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• 239000005751 Copper oxide Substances 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• 102000004674 D-amino-acid oxidase Human genes 0.000 description 1
• 108010003989 D-amino-acid oxidase Proteins 0.000 description 1
• 208000024254 Delusional disease Diseases 0.000 description 1
• 208000016192 Demyelinating disease Diseases 0.000 description 1
• 206010012374 Depressed mood Diseases 0.000 description 1
• 206010054089 Depressive symptom Diseases 0.000 description 1
• HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 206010012735 Diarrhoea Diseases 0.000 description 1
• 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 1
• 206010013496 Disturbance in attention Diseases 0.000 description 1
• 206010013647 Drowning Diseases 0.000 description 1
• 206010013654 Drug abuse Diseases 0.000 description 1
• 208000000059 Dyspnea Diseases 0.000 description 1
• 206010013975 Dyspnoeas Diseases 0.000 description 1
• 208000014094 Dystonic disease Diseases 0.000 description 1
• 208000030814 Eating disease Diseases 0.000 description 1
• 206010014557 Emotional poverty Diseases 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 241001539473 Euphoria Species 0.000 description 1
• 206010015535 Euphoric mood Diseases 0.000 description 1
• 208000019454 Feeding and Eating disease Diseases 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 201000011240 Frontotemporal dementia Diseases 0.000 description 1
• 108091006027 G proteins Proteins 0.000 description 1
• 102000030782 GTP binding Human genes 0.000 description 1
• 108091000058 GTP-Binding Proteins 0.000 description 1
• 208000034826 Genetic Predisposition to Disease 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
• 102100030652 Glutamate receptor 1 Human genes 0.000 description 1
• 101710087628 Glutamate receptor 1 Proteins 0.000 description 1
• 102000010726 Glycine Plasma Membrane Transport Proteins Human genes 0.000 description 1
• 108010063380 Glycine Plasma Membrane Transport Proteins Proteins 0.000 description 1
• 208000034308 Grand mal convulsion Diseases 0.000 description 1
• WYCLKVQLVUQKNZ-UHFFFAOYSA-N Halazepam Chemical compound N=1CC(=O)N(CC(F)(F)F)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 WYCLKVQLVUQKNZ-UHFFFAOYSA-N 0.000 description 1
• 208000004547 Hallucinations Diseases 0.000 description 1
• 206010019196 Head injury Diseases 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 208000010496 Heart Arrest Diseases 0.000 description 1
• 208000008454 Hyperhidrosis Diseases 0.000 description 1
• 206010021030 Hypomania Diseases 0.000 description 1
• 206010021133 Hypoventilation Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 208000004404 Intractable Pain Diseases 0.000 description 1
• 102000006541 Ionotropic Glutamate Receptors Human genes 0.000 description 1
• 108010008812 Ionotropic Glutamate Receptors Proteins 0.000 description 1
• 206010022998 Irritability Diseases 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• 208000020358 Learning disease Diseases 0.000 description 1
• 206010024264 Lethargy Diseases 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 208000003863 Marijuana Abuse Diseases 0.000 description 1
• ZPXSCAKFGYXMGA-UHFFFAOYSA-N Mazindol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=C(Cl)C=C1 ZPXSCAKFGYXMGA-UHFFFAOYSA-N 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• 206010027374 Mental impairment Diseases 0.000 description 1
• 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 1
• 102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 description 1
• DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 1
• UEQUQVLFIPOEMF-UHFFFAOYSA-N Mianserin Chemical compound C1C2=CC=CC=C2N2CCN(C)CC2C2=CC=CC=C21 UEQUQVLFIPOEMF-UHFFFAOYSA-N 0.000 description 1
• 208000019695 Migraine disease Diseases 0.000 description 1
• 206010027940 Mood altered Diseases 0.000 description 1
• 208000019430 Motor disease Diseases 0.000 description 1
• 208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000008238 Muscle Spasticity Diseases 0.000 description 1
• 206010049816 Muscle tightness Diseases 0.000 description 1
• 206010028347 Muscle twitching Diseases 0.000 description 1
• 206010028403 Mutism Diseases 0.000 description 1
• 208000002033 Myoclonus Diseases 0.000 description 1
• 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 1
• 229940095474 NMDA agonist Drugs 0.000 description 1
• 206010028813 Nausea Diseases 0.000 description 1
• 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 108010040718 Neurokinin-1 Receptors Proteins 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• 206010029412 Nightmare Diseases 0.000 description 1
• KYYIDSXMWOZKMP-UHFFFAOYSA-N O-desmethylvenlafaxine Chemical compound C1CCCCC1(O)C(CN(C)C)C1=CC=C(O)C=C1 KYYIDSXMWOZKMP-UHFFFAOYSA-N 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 206010052794 Panic disorder with agoraphobia Diseases 0.000 description 1
• 206010033864 Paranoia Diseases 0.000 description 1
• 208000027089 Parkinsonian disease Diseases 0.000 description 1
• 206010034010 Parkinsonism Diseases 0.000 description 1
• AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 241000009328 Perro Species 0.000 description 1
• RMUCZJUITONUFY-UHFFFAOYSA-N Phenelzine Chemical compound NNCCC1=CC=CC=C1 RMUCZJUITONUFY-UHFFFAOYSA-N 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
• LHNKBXRFNPMIBR-UHFFFAOYSA-N Picrotoxin Natural products CC(C)(O)C1(O)C2OC(=O)C1C3(O)C4OC4C5C(=O)OC2C35C LHNKBXRFNPMIBR-UHFFFAOYSA-N 0.000 description 1
• 206010065016 Post-traumatic pain Diseases 0.000 description 1
• 201000010769 Prader-Willi syndrome Diseases 0.000 description 1
• MWQCHHACWWAQLJ-UHFFFAOYSA-N Prazepam Chemical compound O=C1CN=C(C=2C=CC=CC=2)C2=CC(Cl)=CC=C2N1CC1CC1 MWQCHHACWWAQLJ-UHFFFAOYSA-N 0.000 description 1
• 206010036618 Premenstrual syndrome Diseases 0.000 description 1
• 208000001431 Psychomotor Agitation Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• 206010038743 Restlessness Diseases 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• 208000036353 Rett disease Diseases 0.000 description 1
• XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
• 208000030988 Schizoid Personality disease Diseases 0.000 description 1
• 208000020186 Schizophreniform disease Diseases 0.000 description 1
• 208000024791 Schizotypal Personality disease Diseases 0.000 description 1
• 206010039917 Selective mutism Diseases 0.000 description 1
• 208000000810 Separation Anxiety Diseases 0.000 description 1
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
• 206010041243 Social avoidant behaviour Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
• 231100000643 Substance intoxication Toxicity 0.000 description 1
• 102100037346 Substance-P receptor Human genes 0.000 description 1
• 208000034972 Sudden Infant Death Diseases 0.000 description 1
• 206010042440 Sudden infant death syndrome Diseases 0.000 description 1
• 206010065604 Suicidal behaviour Diseases 0.000 description 1
• 206010042464 Suicide attempt Diseases 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• GFBKORZTTCHDGY-UWVJOHFNSA-N Thiothixene Chemical compound C12=CC(S(=O)(=O)N(C)C)=CC=C2SC2=CC=CC=C2\C1=C\CCN1CCN(C)CC1 GFBKORZTTCHDGY-UWVJOHFNSA-N 0.000 description 1
• 206010043994 Tonic convulsion Diseases 0.000 description 1
• KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
• 208000031674 Traumatic Acute Stress disease Diseases 0.000 description 1
• 206010044565 Tremor Diseases 0.000 description 1
• HWHLPVGTWGOCJO-UHFFFAOYSA-N Trihexyphenidyl Chemical group C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 HWHLPVGTWGOCJO-UHFFFAOYSA-N 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 201000004810 Vascular dementia Diseases 0.000 description 1
• LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 208000005298 acute pain Diseases 0.000 description 1
• 208000026345 acute stress disease Diseases 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• 208000028505 alcohol-related disease Diseases 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 201000011068 alcoholic psychosis Diseases 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 229940125516 allosteric modulator Drugs 0.000 description 1
• DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
• 229960003805 amantadine Drugs 0.000 description 1
• 229960000836 amitriptyline Drugs 0.000 description 1
• KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 230000006986 amnesia Effects 0.000 description 1
• 229960001301 amobarbital Drugs 0.000 description 1
• 229960002519 amoxapine Drugs 0.000 description 1
• QWGDMFLQWFTERH-UHFFFAOYSA-N amoxapine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2N=C1N1CCNCC1 QWGDMFLQWFTERH-UHFFFAOYSA-N 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 230000008503 anti depressant like effect Effects 0.000 description 1
• 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
• 239000000739 antihistaminic agent Substances 0.000 description 1
• 229940125715 antihistaminic agent Drugs 0.000 description 1
• 229940005530 anxiolytics Drugs 0.000 description 1
• 230000004596 appetite loss Effects 0.000 description 1
• ATALOFNDEOCMKK-OITMNORJSA-N aprepitant Chemical compound O([C@@H]([C@@H]1C=2C=CC(F)=CC=2)O[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CCN1CC1=NNC(=O)N1 ATALOFNDEOCMKK-OITMNORJSA-N 0.000 description 1
• 229960001372 aprepitant Drugs 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 208000025748 atypical depressive disease Diseases 0.000 description 1
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
• GIJXKZJWITVLHI-PMOLBWCYSA-N benzatropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(C=1C=CC=CC=1)C1=CC=CC=C1 GIJXKZJWITVLHI-PMOLBWCYSA-N 0.000 description 1
• 229960001081 benzatropine Drugs 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 229960003003 biperiden Drugs 0.000 description 1
• YSXKPIUOCJLQIE-UHFFFAOYSA-N biperiden Chemical compound C1C(C=C2)CC2C1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 YSXKPIUOCJLQIE-UHFFFAOYSA-N 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• 229960002495 buspirone Drugs 0.000 description 1
• QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 1
• 229940015694 butabarbital Drugs 0.000 description 1
• 229960004301 butriptyline Drugs 0.000 description 1
• ALELTFCQZDXAMQ-UHFFFAOYSA-N butriptyline Chemical compound C1CC2=CC=CC=C2C(CC(C)CN(C)C)C2=CC=CC=C21 ALELTFCQZDXAMQ-UHFFFAOYSA-N 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 230000009460 calcium influx Effects 0.000 description 1
• 230000003185 calcium uptake Effects 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 229960000623 carbamazepine Drugs 0.000 description 1
• FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 229960004782 chlordiazepoxide Drugs 0.000 description 1
• ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 1
• 239000000064 cholinergic agonist Substances 0.000 description 1
• 239000000812 cholinergic antagonist Substances 0.000 description 1
• 208000012601 choreatic disease Diseases 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 230000037326 chronic stress Effects 0.000 description 1
• 229960001653 citalopram Drugs 0.000 description 1
• 229960004606 clomipramine Drugs 0.000 description 1
• 229960003120 clonazepam Drugs 0.000 description 1
• DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 1
• 229960004362 clorazepate Drugs 0.000 description 1
• XDDJGVMJFWAHJX-UHFFFAOYSA-M clorazepic acid anion Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(C(=O)[O-])N=C1C1=CC=CC=C1 XDDJGVMJFWAHJX-UHFFFAOYSA-M 0.000 description 1
• 229960003920 cocaine Drugs 0.000 description 1
• 230000003931 cognitive performance Effects 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000013066 combination product Substances 0.000 description 1
• 229940127555 combination product Drugs 0.000 description 1
• 238000004891 communication Methods 0.000 description 1
• 229940125773 compound 10 Drugs 0.000 description 1
• 229940125797 compound 12 Drugs 0.000 description 1
• 229940126543 compound 14 Drugs 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 229940126142 compound 16 Drugs 0.000 description 1
• 229940126208 compound 22 Drugs 0.000 description 1
• 229940125877 compound 31 Drugs 0.000 description 1
• 238000013329 compounding Methods 0.000 description 1
• 230000021615 conjugation Effects 0.000 description 1
• 239000003179 convulsant agent Substances 0.000 description 1
• 229910000431 copper oxide Inorganic materials 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 230000001054 cortical effect Effects 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• BOCUKUHCLICSIY-QJWLJZLASA-N cyclothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2C1[C@H](C=C2)C[C@H]2C1 BOCUKUHCLICSIY-QJWLJZLASA-N 0.000 description 1
• 229960003176 cyclothiazide Drugs 0.000 description 1
• 208000026725 cyclothymic disease Diseases 0.000 description 1
• 230000009849 deactivation Effects 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 230000003412 degenerative effect Effects 0.000 description 1
• 230000000994 depressogenic effect Effects 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 229960003914 desipramine Drugs 0.000 description 1
• 229960001623 desvenlafaxine Drugs 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 229960003529 diazepam Drugs 0.000 description 1
• AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 238000002050 diffraction method Methods 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
• 229960000520 diphenhydramine Drugs 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
• 235000014632 disordered eating Nutrition 0.000 description 1
• 239000003372 dissociative anesthetic agent Substances 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 208000002173 dizziness Diseases 0.000 description 1
• 239000000221 dopamine uptake inhibitor Substances 0.000 description 1
• 230000003291 dopaminomimetic effect Effects 0.000 description 1
• 229960001393 dosulepin Drugs 0.000 description 1
• 229960005426 doxepin Drugs 0.000 description 1
• ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 201000002545 drug psychosis Diseases 0.000 description 1
• 239000003596 drug target Substances 0.000 description 1
• 206010013781 dry mouth Diseases 0.000 description 1
• 229960002866 duloxetine Drugs 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 230000008482 dysregulation Effects 0.000 description 1
• 208000010118 dystonia Diseases 0.000 description 1
• 238000002001 electrophysiology Methods 0.000 description 1
• 230000007831 electrophysiology Effects 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 206010015037 epilepsy Diseases 0.000 description 1
• 229960004341 escitalopram Drugs 0.000 description 1
• WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
• 230000002964 excitative effect Effects 0.000 description 1
• 230000028023 exocytosis Effects 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 231100000040 eye damage Toxicity 0.000 description 1
• PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 1
• 229960002428 fentanyl Drugs 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 229950003678 flesinoxan Drugs 0.000 description 1
• NYSDRDDQELAVKP-SFHVURJKSA-N flesinoxan Chemical compound C([C@@H](O1)CO)OC2=C1C=CC=C2N(CC1)CCN1CCNC(=O)C1=CC=C(F)C=C1 NYSDRDDQELAVKP-SFHVURJKSA-N 0.000 description 1
• 238000000799 fluorescence microscopy Methods 0.000 description 1
• 229960002464 fluoxetine Drugs 0.000 description 1
• 229960004038 fluvoxamine Drugs 0.000 description 1
• CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 1
• 230000004907 flux Effects 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 238000012048 forced swim test Methods 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 229960002870 gabapentin Drugs 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 238000010353 genetic engineering Methods 0.000 description 1
• 229960000647 gepirone Drugs 0.000 description 1
• QOIGKGMMAGJZNZ-UHFFFAOYSA-N gepirone Chemical compound O=C1CC(C)(C)CC(=O)N1CCCCN1CCN(C=2N=CC=CN=2)CC1 QOIGKGMMAGJZNZ-UHFFFAOYSA-N 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 229960002158 halazepam Drugs 0.000 description 1
• 230000003400 hallucinatory effect Effects 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 125000001475 halogen functional group Chemical group 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 230000005802 health problem Effects 0.000 description 1
• 210000003494 hepatocyte Anatomy 0.000 description 1
• 230000000971 hippocampal effect Effects 0.000 description 1
• 210000004295 hippocampal neuron Anatomy 0.000 description 1
• 102000053576 human ABCB1 Human genes 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 206010020765 hypersomnia Diseases 0.000 description 1
• 208000003532 hypothyroidism Diseases 0.000 description 1
• 230000002989 hypothyroidism Effects 0.000 description 1
• 229960004801 imipramine Drugs 0.000 description 1
• BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 150000002468 indanes Chemical class 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 230000010354 integration Effects 0.000 description 1
• 230000003933 intellectual function Effects 0.000 description 1
• 230000035987 intoxication Effects 0.000 description 1
• 231100000566 intoxication Toxicity 0.000 description 1
• 229940125425 inverse agonist Drugs 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 229960002844 iprindole Drugs 0.000 description 1
• PLIGPBGDXASWPX-UHFFFAOYSA-N iprindole Chemical compound C1CCCCCC2=C1N(CCCN(C)C)C1=CC=CC=C12 PLIGPBGDXASWPX-UHFFFAOYSA-N 0.000 description 1
• 229950003599 ipsapirone Drugs 0.000 description 1
• 230000001788 irregular Effects 0.000 description 1
• 229960002672 isocarboxazid Drugs 0.000 description 1
• 230000000155 isotopic effect Effects 0.000 description 1
• RPCVIAXDAUMJJP-PZBABLGHSA-N ispronicline Chemical compound CN[C@@H](C)C\C=C\C1=CN=CC(OC(C)C)=C1 RPCVIAXDAUMJJP-PZBABLGHSA-N 0.000 description 1
• 229950001646 ispronicline Drugs 0.000 description 1
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 1
• 229960001848 lamotrigine Drugs 0.000 description 1
• 230000008449 language Effects 0.000 description 1
• 201000003723 learning disability Diseases 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 229960000685 levomilnacipran Drugs 0.000 description 1
• 239000008263 liquid aerosol Substances 0.000 description 1
• 210000001853 liver microsome Anatomy 0.000 description 1
• 229960002813 lofepramine Drugs 0.000 description 1
• SAPNXPWPAUFAJU-UHFFFAOYSA-N lofepramine Chemical compound C12=CC=CC=C2CCC2=CC=CC=C2N1CCCN(C)CC(=O)C1=CC=C(Cl)C=C1 SAPNXPWPAUFAJU-UHFFFAOYSA-N 0.000 description 1
• 208000019017 loss of appetite Diseases 0.000 description 1
• 235000021266 loss of appetite Nutrition 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 210000005171 mammalian brain Anatomy 0.000 description 1
• 229960004090 maprotiline Drugs 0.000 description 1
• QSLMDECMDJKHMQ-GSXCWMCISA-N maprotiline Chemical compound C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 description 1
• 229960002505 maropitant Drugs 0.000 description 1
• 229960000299 mazindol Drugs 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 201000003995 melancholia Diseases 0.000 description 1
• BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
• 229960004640 memantine Drugs 0.000 description 1
• 206010027175 memory impairment Diseases 0.000 description 1
• 230000003340 mental effect Effects 0.000 description 1
• ALARQZQTBTVLJV-UHFFFAOYSA-N mephobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)N(C)C1=O ALARQZQTBTVLJV-UHFFFAOYSA-N 0.000 description 1
• 208000030159 metabolic disease Diseases 0.000 description 1
• 102000006239 metabotropic receptors Human genes 0.000 description 1
• 108020004083 metabotropic receptors Proteins 0.000 description 1
• FBBDOOHMGLLEGJ-UHFFFAOYSA-N methane;hydrochloride Chemical compound C.Cl FBBDOOHMGLLEGJ-UHFFFAOYSA-N 0.000 description 1
• 229960001344 methylphenidate Drugs 0.000 description 1
• 229960001703 methylphenobarbital Drugs 0.000 description 1
• 229960003955 mianserin Drugs 0.000 description 1
• 206010027599 migraine Diseases 0.000 description 1
• 229960000600 milnacipran Drugs 0.000 description 1
• 229960001785 mirtazapine Drugs 0.000 description 1
• RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• YHXISWVBGDMDLQ-UHFFFAOYSA-N moclobemide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCCN1CCOCC1 YHXISWVBGDMDLQ-UHFFFAOYSA-N 0.000 description 1
• 229960004644 moclobemide Drugs 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 235000013923 monosodium glutamate Nutrition 0.000 description 1
• 230000007510 mood change Effects 0.000 description 1
• 229940127237 mood stabilizer Drugs 0.000 description 1
• 239000004050 mood stabilizer Substances 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• 239000003706 n methyl dextro aspartic acid receptor stimulating agent Substances 0.000 description 1
• CMRLNEYJEPELSM-BTQNPOSSSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1h-indazole-3-carboxamide;hydrochloride Chemical compound Cl.C1=CC=C2C(C(N[C@H]3C4CCN(CC4)C3)=O)=NNC2=C1 CMRLNEYJEPELSM-BTQNPOSSSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 201000003631 narcolepsy Diseases 0.000 description 1
• 230000008693 nausea Effects 0.000 description 1
• 208000004296 neuralgia Diseases 0.000 description 1
• 239000003176 neuroleptic agent Substances 0.000 description 1
• 230000000701 neuroleptic effect Effects 0.000 description 1
• 230000008555 neuronal activation Effects 0.000 description 1
• 230000008062 neuronal firing Effects 0.000 description 1
• 208000021722 neuropathic pain Diseases 0.000 description 1
• 239000002581 neurotoxin Substances 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 229960002715 nicotine Drugs 0.000 description 1
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
• 230000036565 night sweats Effects 0.000 description 1
• 206010029410 night sweats Diseases 0.000 description 1
• 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 208000001797 obstructive sleep apnea Diseases 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 229940127240 opiate Drugs 0.000 description 1
• 201000005040 opiate dependence Diseases 0.000 description 1
• 201000000988 opioid abuse Diseases 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 229940053544 other antidepressants in atc Drugs 0.000 description 1
• 229960004535 oxazepam Drugs 0.000 description 1
• ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 238000013149 parallel artificial membrane permeability assay Methods 0.000 description 1
• 208000002851 paranoid schizophrenia Diseases 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 229960002296 paroxetine Drugs 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 229960000761 pemoline Drugs 0.000 description 1
• NRNCYVBFPDDJNE-UHFFFAOYSA-N pemoline Chemical compound O1C(N)=NC(=O)C1C1=CC=CC=C1 NRNCYVBFPDDJNE-UHFFFAOYSA-N 0.000 description 1
• 229960001412 pentobarbital Drugs 0.000 description 1
• 230000008447 perception Effects 0.000 description 1
• 208000033300 perinatal asphyxia Diseases 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 208000022821 personality disease Diseases 0.000 description 1
• JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
• 229950010883 phencyclidine Drugs 0.000 description 1
• 229960000964 phenelzine Drugs 0.000 description 1
• 229960002695 phenobarbital Drugs 0.000 description 1
• DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
• 208000019899 phobic disease Diseases 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• VJKUPQSHOVKBCO-AHMKVGDJSA-N picrotoxin Chemical compound O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(=C)C)[C@@H]1C(=O)O2.O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(C)(O)C)[C@@H]1C(=O)O2 VJKUPQSHOVKBCO-AHMKVGDJSA-N 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 210000003538 post-synaptic density Anatomy 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 208000021011 postpartum psychosis Diseases 0.000 description 1
• 108010092804 postsynaptic density proteins Proteins 0.000 description 1
• 230000001242 postsynaptic effect Effects 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
• 229960004856 prazepam Drugs 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 229960005253 procyclidine Drugs 0.000 description 1
• SJMCLWCCNYAWRQ-UHFFFAOYSA-N propane-2-sulfonamide Chemical class CC(C)S(N)(=O)=O SJMCLWCCNYAWRQ-UHFFFAOYSA-N 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 230000004224 protection Effects 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 229960002601 protriptyline Drugs 0.000 description 1
• BWPIARFWQZKAIA-UHFFFAOYSA-N protriptyline Chemical compound C1=CC2=CC=CC=C2C(CCCNC)C2=CC=CC=C21 BWPIARFWQZKAIA-UHFFFAOYSA-N 0.000 description 1
• 239000003368 psychostimulant agent Substances 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 1
• 150000003217 pyrazoles Chemical class 0.000 description 1
• 229960003770 reboxetine Drugs 0.000 description 1
• CBQGYUDMJHNJBX-RTBURBONSA-N reboxetine Chemical compound CCOC1=CC=CC=C1O[C@H](C=1C=CC=CC=1)[C@@H]1OCCNC1 CBQGYUDMJHNJBX-RTBURBONSA-N 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000009877 rendering Methods 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 230000036387 respiratory rate Effects 0.000 description 1
• 229960004136 rivastigmine Drugs 0.000 description 1
• 238000011808 rodent model Methods 0.000 description 1
• 208000022610 schizoaffective disease Diseases 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 229960002060 secobarbital Drugs 0.000 description 1
• KQPKPCNLIDLUMF-UHFFFAOYSA-N secobarbital Chemical compound CCCC(C)C1(CC=C)C(=O)NC(=O)NC1=O KQPKPCNLIDLUMF-UHFFFAOYSA-N 0.000 description 1
• 229960003946 selegiline Drugs 0.000 description 1
• MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 208000025874 separation anxiety disease Diseases 0.000 description 1
• 229960002073 sertraline Drugs 0.000 description 1
• VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
• 231100000872 sexual dysfunction Toxicity 0.000 description 1
• 208000013220 shortness of breath Diseases 0.000 description 1
• 229960004425 sibutramine Drugs 0.000 description 1
• UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 239000002356 single layer Substances 0.000 description 1
• 201000002859 sleep apnea Diseases 0.000 description 1
• 208000020685 sleep-wake disease Diseases 0.000 description 1
• 230000004039 social cognition Effects 0.000 description 1
• 230000003997 social interaction Effects 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 229940073490 sodium glutamate Drugs 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
• 229940084026 sodium valproate Drugs 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 208000018198 spasticity Diseases 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 208000002320 spinal muscular atrophy Diseases 0.000 description 1
• 238000001694 spray drying Methods 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000000021 stimulant Substances 0.000 description 1
• 230000002739 subcortical effect Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 201000009032 substance abuse Diseases 0.000 description 1
• 231100000736 substance abuse Toxicity 0.000 description 1
• 201000006152 substance dependence Diseases 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 230000009747 swallowing Effects 0.000 description 1
• 230000035900 sweating Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000003977 synaptic function Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 229960001685 tacrine Drugs 0.000 description 1
• YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
• 229950011332 talnetant Drugs 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 238000011285 therapeutic regimen Methods 0.000 description 1
• 230000004797 therapeutic response Effects 0.000 description 1
• PBJUNZJWGZTSKL-MRXNPFEDSA-N tiagabine Chemical compound C1=CSC(C(=CCCN2C[C@@H](CCC2)C(O)=O)C2=C(C=CS2)C)=C1C PBJUNZJWGZTSKL-MRXNPFEDSA-N 0.000 description 1
• 229960001918 tiagabine Drugs 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 239000003104 tissue culture media Substances 0.000 description 1
• 230000001256 tonic effect Effects 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229960004394 topiramate Drugs 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000440 toxicity profile Toxicity 0.000 description 1
• 238000012549 training Methods 0.000 description 1
• PHTUQLWOUWZIMZ-GZTJUZNOSA-N trans-dothiepin Chemical compound C1SC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 PHTUQLWOUWZIMZ-GZTJUZNOSA-N 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 229960003741 tranylcypromine Drugs 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 206010044652 trigeminal neuralgia Diseases 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• 229960001032 trihexyphenidyl Drugs 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 1
• 229960004751 varenicline Drugs 0.000 description 1
• 229960001255 viloxazine Drugs 0.000 description 1
• 230000031836 visual learning Effects 0.000 description 1
• 230000016776 visual perception Effects 0.000 description 1
• 230000036642 wellbeing Effects 0.000 description 1