TWI292314B - - Google Patents
Download PDFInfo
- Publication number
- TWI292314B TWI292314B TW90102849A TW90102849A TWI292314B TW I292314 B TWI292314 B TW I292314B TW 90102849 A TW90102849 A TW 90102849A TW 90102849 A TW90102849 A TW 90102849A TW I292314 B TWI292314 B TW I292314B
- Authority
- TW
- Taiwan
- Prior art keywords
- fluorophenyl
- parkinson
- physiologically acceptable
- pharmaceutical composition
- acceptable salt
- Prior art date
Links
- 150000003839 salts Chemical class 0.000 claims description 100
- 238000011282 treatment Methods 0.000 claims description 59
- 239000007921 spray Substances 0.000 claims description 46
- 230000000694 effects Effects 0.000 claims description 38
- 239000008194 pharmaceutical composition Substances 0.000 claims description 35
- 208000011580 syndromic disease Diseases 0.000 claims description 32
- 208000018737 Parkinson disease Diseases 0.000 claims description 30
- 206010044565 Tremor Diseases 0.000 claims description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 23
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical group OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 18
- 230000003902 lesion Effects 0.000 claims description 18
- 230000033001 locomotion Effects 0.000 claims description 18
- 208000014094 Dystonic disease Diseases 0.000 claims description 16
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 16
- 230000002411 adverse Effects 0.000 claims description 16
- 229960004502 levodopa Drugs 0.000 claims description 16
- 208000010118 dystonia Diseases 0.000 claims description 15
- 230000002269 spontaneous effect Effects 0.000 claims description 15
- 206010034010 Parkinsonism Diseases 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 208000002033 Myoclonus Diseases 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 12
- 239000007924 injection Substances 0.000 claims description 11
- 238000002347 injection Methods 0.000 claims description 11
- -1 Methylamine thiol Chemical class 0.000 claims description 10
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 9
- 229940125688 antiparkinson agent Drugs 0.000 claims description 8
- 208000027776 Extrapyramidal disease Diseases 0.000 claims description 6
- 230000000648 anti-parkinson Effects 0.000 claims description 3
- 239000000939 antiparkinson agent Substances 0.000 claims description 3
- 239000003176 neuroleptic agent Substances 0.000 claims description 3
- 239000013589 supplement Substances 0.000 claims description 3
- 238000012937 correction Methods 0.000 claims description 2
- 230000000701 neuroleptic effect Effects 0.000 claims description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 2
- IVTMXOXVAHXCHI-YXLMWLKOSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid;(2s)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid Chemical group OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1.NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 IVTMXOXVAHXCHI-YXLMWLKOSA-N 0.000 claims 1
- 239000000047 product Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 description 36
- 229940079593 drug Drugs 0.000 description 21
- 238000004519 manufacturing process Methods 0.000 description 19
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 15
- 238000010171 animal model Methods 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 206010008748 Chorea Diseases 0.000 description 11
- 208000012601 choreatic disease Diseases 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 10
- 208000012661 Dyskinesia Diseases 0.000 description 9
- 239000000654 additive Substances 0.000 description 9
- 230000000996 additive effect Effects 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 210000005036 nerve Anatomy 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 239000012530 fluid Substances 0.000 description 8
- 241000282693 Cercopithecidae Species 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 206010036790 Productive cough Diseases 0.000 description 7
- 239000002249 anxiolytic agent Substances 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 208000024794 sputum Diseases 0.000 description 7
- 210000003802 sputum Anatomy 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 206010042772 syncope Diseases 0.000 description 7
- 230000009471 action Effects 0.000 description 6
- 229960003638 dopamine Drugs 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 230000001256 tonic effect Effects 0.000 description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 5
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 206010038743 Restlessness Diseases 0.000 description 5
- 208000018839 Wilson disease Diseases 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 206010041232 sneezing Diseases 0.000 description 5
- 125000003396 thiol group Chemical class [H]S* 0.000 description 5
- 108050004812 Dopamine receptor Proteins 0.000 description 4
- 102000015554 Dopamine receptor Human genes 0.000 description 4
- 208000001089 Multiple system atrophy Diseases 0.000 description 4
- 208000001431 Psychomotor Agitation Diseases 0.000 description 4
- 229940035678 anti-parkinson drug Drugs 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000007850 degeneration Effects 0.000 description 4
- 230000003111 delayed effect Effects 0.000 description 4
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 230000004064 dysfunction Effects 0.000 description 4
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 4
- 230000003340 mental effect Effects 0.000 description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- 238000007619 statistical method Methods 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 238000004448 titration Methods 0.000 description 4
- 206010008027 Cerebellar atrophy Diseases 0.000 description 3
- 208000023105 Huntington disease Diseases 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 206010041235 Snoring Diseases 0.000 description 3
- 206010044074 Torticollis Diseases 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 210000001577 neostriatum Anatomy 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 208000020016 psychiatric disease Diseases 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 2
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 2
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 2
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 102000004073 Dopamine D3 Receptors Human genes 0.000 description 2
- 108090000525 Dopamine D3 Receptors Proteins 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 208000010496 Heart Arrest Diseases 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 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 2
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 2
- 235000011613 Pinus brutia Nutrition 0.000 description 2
- 241000018646 Pinus brutia Species 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 229940025084 amphetamine Drugs 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000002973 anti-dopamine Effects 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- BNQDCRGUHNALGH-UHFFFAOYSA-N benserazide Chemical compound OCC(N)C(=O)NNCC1=CC=C(O)C(O)=C1O BNQDCRGUHNALGH-UHFFFAOYSA-N 0.000 description 2
- 229960000911 benserazide Drugs 0.000 description 2
- 229910052797 bismuth Inorganic materials 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 2
- 229960002495 buspirone Drugs 0.000 description 2
- 229960004205 carbidopa Drugs 0.000 description 2
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 description 2
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000002804 dopamine agent Substances 0.000 description 2
- 229940052760 dopamine agonists Drugs 0.000 description 2
- 239000012154 double-distilled water Substances 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 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 2
- 230000001146 hypoxic effect Effects 0.000 description 2
- 208000018197 inherited torticollis Diseases 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 201000010256 myopathy, lactic acidosis, and sideroblastic anemia Diseases 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N pyridine-3-amine Natural products NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000002689 soil Substances 0.000 description 2
- 230000001148 spastic effect Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 1
- 208000000187 Abnormal Reflex Diseases 0.000 description 1
- 206010000599 Acromegaly Diseases 0.000 description 1
- 206010001540 Akathisia Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 240000002900 Arthrospira platensis Species 0.000 description 1
- 235000016425 Arthrospira platensis Nutrition 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000019352 Blepharospasm-oromandibular dystonia syndrome Diseases 0.000 description 1
- 240000008564 Boehmeria nivea Species 0.000 description 1
- 241000255789 Bombyx mori Species 0.000 description 1
- 108030001720 Bontoxilysin Proteins 0.000 description 1
- 206010006100 Bradykinesia Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 241000282461 Canis lupus Species 0.000 description 1
- 241000238366 Cephalopoda Species 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
- 229940123603 Dopamine D2 receptor antagonist Drugs 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000004929 Facial Paralysis Diseases 0.000 description 1
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical group FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 1
- 206010071602 Genetic polymorphism Diseases 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 201000005190 Meige syndrome Diseases 0.000 description 1
- VKEQBMCRQDSRET-UHFFFAOYSA-N Methylone Chemical compound CNC(C)C(=O)C1=CC=C2OCOC2=C1 VKEQBMCRQDSRET-UHFFFAOYSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 101001135571 Mus musculus Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 1
- 206010049816 Muscle tightness Diseases 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 101710141525 Neurotoxin 3 Proteins 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- RSDOPYMFZBJHRL-UHFFFAOYSA-N Oxotremorine Chemical compound O=C1CCCN1CC#CCN1CCCC1 RSDOPYMFZBJHRL-UHFFFAOYSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- 208000005793 Restless legs syndrome Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000555745 Sciuridae Species 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 208000009106 Shy-Drager Syndrome Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 240000003864 Ulex europaeus Species 0.000 description 1
- 235000010730 Ulex europaeus Nutrition 0.000 description 1
- 208000036826 VIIth nerve paralysis Diseases 0.000 description 1
- 208000024453 abnormal involuntary movement Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000011374 additional therapy Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000008484 agonism Effects 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 230000000172 allergic effect Effects 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
- ZMJZYXKPJWGDGR-UHFFFAOYSA-N aminosulfamic acid Chemical compound NNS(O)(=O)=O ZMJZYXKPJWGDGR-UHFFFAOYSA-N 0.000 description 1
- 230000002547 anomalous effect Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000037147 athletic performance Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940053031 botulinum toxin Drugs 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- 229960002452 budipine Drugs 0.000 description 1
- QIHLUZAFSSMXHQ-UHFFFAOYSA-N budipine Chemical compound C1CN(C(C)(C)C)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 QIHLUZAFSSMXHQ-UHFFFAOYSA-N 0.000 description 1
- VVOLTHDYLKNMJL-UHFFFAOYSA-N caberoline Natural products COc1ccc2c(c1)N(C)C3C4CC5C6C(=O)OC5(CN4CCC236)C(C)O VVOLTHDYLKNMJL-UHFFFAOYSA-N 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 201000002866 cervical dystonia Diseases 0.000 description 1
- 230000000739 chaotic effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
- 210000000078 claw Anatomy 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940005501 dopaminergic agent Drugs 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 208000010515 dystocia Diseases 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 229960003337 entacapone Drugs 0.000 description 1
- JRURYQJSLYLRLN-BJMVGYQFSA-N entacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-BJMVGYQFSA-N 0.000 description 1
- 229960003133 ergot alkaloid Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 206010020745 hyperreflexia Diseases 0.000 description 1
- 230000035859 hyperreflexia Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 229940025708 injectable product Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000003447 ipsilateral effect Effects 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 239000010450 olivine Substances 0.000 description 1
- 229910052609 olivine Inorganic materials 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 208000027714 reflex symptom Diseases 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960001879 ropinirole Drugs 0.000 description 1
- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 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
- 229960003946 selegiline Drugs 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 230000007958 sleep Effects 0.000 description 1
- 230000003997 social interaction Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229940082787 spirulina Drugs 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- FZUJWWOKDIGOKH-UHFFFAOYSA-N sulfuric acid hydrochloride Chemical compound Cl.OS(O)(=O)=O FZUJWWOKDIGOKH-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 229960004603 tolcapone Drugs 0.000 description 1
- MIQPIUSUKVNLNT-UHFFFAOYSA-N tolcapone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC(O)=C(O)C([N+]([O-])=O)=C1 MIQPIUSUKVNLNT-UHFFFAOYSA-N 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 235000012184 tortilla Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000028838 turning behavior Effects 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW90102849A TWI292314B (enExample) | 2001-02-09 | 2001-02-09 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW90102849A TWI292314B (enExample) | 2001-02-09 | 2001-02-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TWI292314B true TWI292314B (enExample) | 2008-01-11 |
Family
ID=45067490
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW90102849A TWI292314B (enExample) | 2001-02-09 | 2001-02-09 |
Country Status (1)
| Country | Link |
|---|---|
| TW (1) | TWI292314B (enExample) |
-
2001
- 2001-02-09 TW TW90102849A patent/TWI292314B/zh not_active IP Right Cessation
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102274517B (zh) | 治疗帕金森病的方法 | |
| AU685510B2 (en) | Potentiation of drug response | |
| US6232326B1 (en) | Treatment for schizophrenia and other dopamine system dysfunctions | |
| AU2003284005B2 (en) | Dosage escalation and divided daily dose of anti-depressants to treat neurological disorders | |
| US20090137565A1 (en) | Method for treatment of movement disorders | |
| JP2020530847A (ja) | プリドピジンによる筋萎縮性側索硬化症の治療方法 | |
| EP1696905A1 (de) | Verwendung von substituierten 2-aminotetralinen zur vorbeugenden behandlung von morbus parkinson | |
| JP6137833B2 (ja) | 脱髄性および他の神経系疾患を患っている患者における神経認知的および／または神経精神医学的障害を改善するための４−アミノピリジンの使用 | |
| TW201841637A (zh) | 使用ccr3-抑制劑治療老化相關損傷之方法及組合物 | |
| WO2021030607A1 (en) | Pimavanserin for treating neurodegenerative diseases | |
| KR100830139B1 (ko) | (ｒ)-(-)-2-[５-(４-플루오로페닐)-３-피리딜메틸아미노메틸]-크로만 및 이의 생리학적으로 허용가능한 염의 신규한 용도 | |
| EA015483B1 (ru) | ПРИМЕНЕНИЕ ИНГИБИТОРА p38 КИНАЗЫ ДЛЯ ЛЕЧЕНИЯ ПСИХИАТРИЧЕСКИХ РАССТРОЙСТВ | |
| JP2022031814A (ja) | 不安障害を治療するための（２Ｓ）－１－［４－（３，４－ジクロロフェニル）ピペリジン－１－イル］－３－［２－（５－メチル－１，３，４－オキサジアゾール－２－イル）ベンゾ［ｂ］フラン－４－イルオキシ］プロパン－２－オールまたはその代謝産物 | |
| TWI292314B (enExample) | ||
| JP2004538289A (ja) | ２−［５−（４−フルオロフェニル）−３−ピリジルメチルアミノメチル］−クロマンおよびその生理学的に許容し得る塩の新規な使用 | |
| RU2320336C2 (ru) | Новое применение замещенных аминометилхроманов для лечения нарушений движений или нежелательных действий, вызываемых средствами, которые вводятся для лечения экстрапирамидных нарушений движений | |
| JP2942626B2 (ja) | 神経学的疾患を治療するための４，４′―〔９ｈ―フルオレン―９―イリデンビス（メチレン）〕ビスピリミジン | |
| WO2024102802A1 (en) | Zelatriazin for the treatment of depression | |
| Maan | Comparison of Methamphetamine and MDMA Extended Access Self-administration: Acquisition, Maintenance, and Response Patterns | |
| Zare et al. | Wake-Promoting agents; insights into clinical use and molecular perspectives | |
| DE10157673A1 (de) | Verwendung von N-(Indolcarbonyl-)piperazinderivaten | |
| JPS6241208B2 (enExample) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |