HU217124B - Eljárás (S)-(-)-alfa-etil-2-oxo-1-pirrolidin-acetamid-tartalmú, szorongás oldására alkalmas gyógyászati készítmények előállítására - Google Patents
Eljárás (S)-(-)-alfa-etil-2-oxo-1-pirrolidin-acetamid-tartalmú, szorongás oldására alkalmas gyógyászati készítmények előállítására Download PDFInfo
- Publication number
- HU217124B HU217124B HU9402704A HU9402704A HU217124B HU 217124 B HU217124 B HU 217124B HU 9402704 A HU9402704 A HU 9402704A HU 9402704 A HU9402704 A HU 9402704A HU 217124 B HU217124 B HU 217124B
- Authority
- HU
- Hungary
- Prior art keywords
- anxiety
- animals
- oxo
- compound
- formula
- Prior art date
Links
- 208000019901 Anxiety disease Diseases 0.000 title claims abstract description 50
- 230000036506 anxiety Effects 0.000 title claims abstract description 40
- 238000011282 treatment Methods 0.000 title claims abstract description 19
- 238000000034 method Methods 0.000 title claims description 29
- 230000008569 process Effects 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 title description 26
- 239000003814 drug Substances 0.000 claims abstract description 10
- 230000037396 body weight Effects 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 239000004480 active ingredient Substances 0.000 claims description 15
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 229940125713 antianxiety drug Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 3
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims 1
- HPHUVLMMVZITSG-LURJTMIESA-N levetiracetam Chemical compound CC[C@@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-LURJTMIESA-N 0.000 abstract description 4
- 241001465754 Metazoa Species 0.000 description 89
- 150000001875 compounds Chemical class 0.000 description 69
- 238000012360 testing method Methods 0.000 description 42
- 229960004782 chlordiazepoxide Drugs 0.000 description 27
- 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 26
- 230000000949 anxiolytic effect Effects 0.000 description 22
- 230000004044 response Effects 0.000 description 21
- 230000000694 effects Effects 0.000 description 19
- 230000035882 stress Effects 0.000 description 17
- 238000003556 assay Methods 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 239000002249 anxiolytic agent Substances 0.000 description 11
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 10
- 150000001557 benzodiazepines Chemical class 0.000 description 9
- 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 9
- 229960003529 diazepam Drugs 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 230000006399 behavior Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 5
- 230000003109 amnesic effect Effects 0.000 description 5
- 230000003542 behavioural effect Effects 0.000 description 5
- 229940049706 benzodiazepine Drugs 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 239000007928 intraperitoneal injection Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000002887 neurotoxic effect Effects 0.000 description 5
- 230000001575 pathological effect Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 206010021118 Hypotonia Diseases 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 210000003027 ear inner Anatomy 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000036640 muscle relaxation Effects 0.000 description 4
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 206010003591 Ataxia Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000036626 alertness Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 230000002996 emotional effect Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000011514 reflex Effects 0.000 description 3
- 238000012453 sprague-dawley rat model Methods 0.000 description 3
- 238000012549 training Methods 0.000 description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 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
- 238000011785 NMRI mouse Methods 0.000 description 2
- 206010029350 Neurotoxicity Diseases 0.000 description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 206010039897 Sedation Diseases 0.000 description 2
- 206010044221 Toxic encephalopathy Diseases 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 206010048010 Withdrawal syndrome Diseases 0.000 description 2
- 230000008649 adaptation response Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000001353 anxiety effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229940057948 magnesium stearate Drugs 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 230000001095 motoneuron effect Effects 0.000 description 2
- 231100000189 neurotoxic Toxicity 0.000 description 2
- 231100000228 neurotoxicity Toxicity 0.000 description 2
- 230000007135 neurotoxicity Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000008447 perception Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000036280 sedation Effects 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229940037128 systemic glucocorticoids Drugs 0.000 description 2
- ZDGXMOZHFUQHKZ-LURJTMIESA-N 2-[(3s)-3-ethyl-2-oxopyrrolidin-1-yl]acetamide Chemical compound CC[C@H]1CCN(CC(N)=O)C1=O ZDGXMOZHFUQHKZ-LURJTMIESA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 102000006822 Agouti Signaling Protein Human genes 0.000 description 1
- 108010072151 Agouti Signaling Protein Proteins 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000031091 Amnestic disease Diseases 0.000 description 1
- 206010002869 Anxiety symptoms Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010010947 Coordination abnormal Diseases 0.000 description 1
- 241000484025 Cuniculus Species 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000011688 Generalised anxiety 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
- 208000008454 Hyperhidrosis Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010034912 Phobia Diseases 0.000 description 1
- 206010037180 Psychiatric symptoms Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000006172 buffering agent Substances 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
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000037870 generalized anxiety Diseases 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 208000016290 incoordination Diseases 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical class CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000003923 mental ability Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000004973 motor coordination Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 230000009907 neuroendocrine response Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000010254 physiological adaptation Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000022832 response to immobilization stress Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000008925 spontaneous activity Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 description 1
- 229960000317 yohimbine Drugs 0.000 description 1
- AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939319732A GB9319732D0 (en) | 1993-09-24 | 1993-09-24 | Use of (s)-alpha-ethyl-2-oxo-l-pyrrolidineacetamide for the treatment of anxiety |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUT68299A HUT68299A (en) | 1995-06-28 |
| HU217124B true HU217124B (hu) | 1999-11-29 |
Family
ID=10742476
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU9402704A HU217124B (hu) | 1993-09-24 | 1994-09-20 | Eljárás (S)-(-)-alfa-etil-2-oxo-1-pirrolidin-acetamid-tartalmú, szorongás oldására alkalmas gyógyászati készítmények előállítására |
Country Status (17)
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5525347A (en) * | 1995-01-31 | 1996-06-11 | Medical University Of South Carolina | Composition and methods for treating performance anxiety |
| TWI238062B (en) | 1999-12-01 | 2005-08-21 | Ucb Sa | A pyrrolidineacetamide derivative alone or in combination for treatment of CNS disorders |
| GB0004297D0 (en) | 2000-02-23 | 2000-04-12 | Ucb Sa | 2-oxo-1 pyrrolidine derivatives process for preparing them and their uses |
| WO2007086891A1 (en) * | 2006-01-24 | 2007-08-02 | Teva Pharmaceutical Industries Ltd. | Levetiracetam formulations and methods for their manufacture |
| WO2007105177A1 (en) * | 2006-03-15 | 2007-09-20 | Actelion Pharmaceuticals Ltd | Tetrahydroisoquinoline derivatives to enhance memory function |
| EP2051696A2 (en) * | 2006-08-18 | 2009-04-29 | Morton Grove Pharmaceuticals, Inc. | Stable liquid levetiracetam compositions and methods |
| BRPI0813218A2 (pt) * | 2007-07-03 | 2014-12-23 | Actelion Pharmaceuticals Ltd | Composto, composição farmacêutica que o contém como princípio ativo e uso do composto. |
| US8288429B2 (en) * | 2007-07-27 | 2012-10-16 | Actelion Pharmaceuticals Ltd. | 2-aza-bicyclo[3.3.0]octane derivatives |
| CA2740610C (en) * | 2008-10-16 | 2020-01-07 | The Johns Hopkins University | Synaptic vesicle protein 2a inhibitors for treating age-related cognitive impairment |
| US8191547B2 (en) * | 2008-10-23 | 2012-06-05 | S-2Tech Llc | Portable solar-heating system having an inflatable solar collector |
| US20100172979A1 (en) * | 2008-12-24 | 2010-07-08 | Zhongshui Yu | Controlled-release formulations |
| US20100159009A1 (en) * | 2008-12-24 | 2010-06-24 | Zhongshui Yu | Controlled-release formulations |
| CA2789014C (en) * | 2010-02-09 | 2019-01-15 | Michela Gallagher | Methods and compositions for improving cognitive function |
| US20120214859A1 (en) * | 2011-02-09 | 2012-08-23 | Michela Gallagher | Methods and compositions for improving cognitive function |
| CA2891122C (en) | 2012-11-14 | 2021-07-20 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| EP2968220B1 (en) | 2013-03-15 | 2021-05-05 | Agenebio, Inc. | Methods and compositions for improving cognitive function |
| US10806717B2 (en) | 2013-03-15 | 2020-10-20 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| US10925834B2 (en) | 2015-05-22 | 2021-02-23 | Agenebio, Inc. | Extended release pharmaceutical compositions of levetiracetam |
| MX2021006243A (es) * | 2018-12-04 | 2021-08-11 | Metys Pharmaceuticals AG | Composiciones sinergicas que comprenden (r)-2-(2-oxopirrolidin-1-i l)butanamida y (s)-2-(2-oxopirrolidin-1-il)butanamida en una proporcion no racemica. |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1414845A1 (ru) * | 1984-03-23 | 1988-08-07 | Всесоюзный Научно-Исследовательский Химико-Фармацевтический Институт Им.С.Орджоникидзе | 1-Тиокарбамоилметилпирролидин-2-тион,обладающий ноотропной активностью, и способ его получени |
| GB8412357D0 (en) * | 1984-05-15 | 1984-06-20 | Ucb Sa | Pharmaceutical composition |
| SU1320707A1 (ru) * | 1985-01-24 | 1987-06-30 | Ивано-Франковский Институт Нефти И Газа | Способ определени износостойкости материалов ма тниковым склерометром |
| GB8827389D0 (en) | 1988-11-23 | 1988-12-29 | Ucb Sa | Process for preparation of(s)alpha-ethyl-2-oxo-1-pyrrolidineacetamide |
| EP0408782A1 (en) * | 1989-07-18 | 1991-01-23 | Nauchnoissledovatelski Chimikopharmatzevtichen Institut | Antihypoxic agent |
| CA2048003A1 (en) * | 1990-08-21 | 1992-02-22 | Serge Burner | Tricyclic pyridone derivatives |
-
1993
- 1993-09-24 GB GB939319732A patent/GB9319732D0/en active Pending
-
1994
- 1994-09-20 HU HU9402704A patent/HU217124B/hu not_active IP Right Cessation
- 1994-09-20 US US08/309,186 patent/US5447952A/en not_active Expired - Lifetime
- 1994-09-20 CA CA002132509A patent/CA2132509A1/en not_active Abandoned
- 1994-09-21 ES ES94870152T patent/ES2145818T3/es not_active Expired - Lifetime
- 1994-09-21 SG SG9502212A patent/SG86284A1/en unknown
- 1994-09-21 DE DE69424009T patent/DE69424009T2/de not_active Expired - Lifetime
- 1994-09-21 NZ NZ264506A patent/NZ264506A/en unknown
- 1994-09-21 AT AT94870152T patent/ATE191849T1/de not_active IP Right Cessation
- 1994-09-21 TW TW083108691A patent/TW283642B/zh active
- 1994-09-21 EP EP94870152A patent/EP0645139B1/fr not_active Expired - Lifetime
- 1994-09-22 JP JP22833194A patent/JP3688735B2/ja not_active Expired - Fee Related
- 1994-09-22 AU AU74169/94A patent/AU672334B2/en not_active Ceased
- 1994-09-22 NO NO943521A patent/NO943521L/no unknown
- 1994-09-23 RU RU94034109A patent/RU2142274C1/ru active
- 1994-09-23 ZA ZA947444A patent/ZA947444B/xx unknown
- 1994-09-23 KR KR1019940024170A patent/KR950007848A/ko not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA2132509A1 (en) | 1995-03-25 |
| ES2145818T3 (es) | 2000-07-16 |
| GB9319732D0 (en) | 1993-11-10 |
| US5447952A (en) | 1995-09-05 |
| DE69424009D1 (de) | 2000-05-25 |
| SG86284A1 (en) | 2002-02-19 |
| NO943521D0 (no) | 1994-09-22 |
| NZ264506A (en) | 1997-09-22 |
| AU672334B2 (en) | 1996-09-26 |
| JP3688735B2 (ja) | 2005-08-31 |
| JPH07149639A (ja) | 1995-06-13 |
| EP0645139B1 (fr) | 2000-04-19 |
| KR950007848A (ko) | 1995-04-15 |
| HUT68299A (en) | 1995-06-28 |
| DE69424009T2 (de) | 2000-09-14 |
| AU7416994A (en) | 1995-04-06 |
| ZA947444B (en) | 1995-05-11 |
| NO943521L (no) | 1995-03-27 |
| TW283642B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1996-08-21 |
| ATE191849T1 (de) | 2000-05-15 |
| EP0645139A1 (fr) | 1995-03-29 |
| RU2142274C1 (ru) | 1999-12-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HU217124B (hu) | Eljárás (S)-(-)-alfa-etil-2-oxo-1-pirrolidin-acetamid-tartalmú, szorongás oldására alkalmas gyógyászati készítmények előállítására | |
| AU743609B2 (en) | Use of cholinesterase inhibitors to treat disorders of attention | |
| US5336675A (en) | Method of treating mania in humans | |
| CA1284952C (en) | Use of specific n-methyl-d-aspartate receptor antagonists in the prevention and treatment of neurodegeneration | |
| US20030147975A1 (en) | Pharmaceutical composition which produces irritation | |
| AU2006256954A1 (en) | Use op brivaracetam for the treatment of diseases characterized by progressive myoclonic epilepsy | |
| Bout et al. | Antischistosomal effect of cyclosporin A: cure and prevention of mouse and rat schistosomiasis mansoni | |
| Ashton | Risks of dependence on benzodiazepine drugs: a major problem of long term treatment | |
| US20040266659A1 (en) | Substances that enhance recall and lucidity during dreaming | |
| SK152897A3 (en) | Use of gabapentin compositions for production of a medicament | |
| JPH0354922B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| Robinson et al. | The effect of M1 muscarinic blockade on behavior and physiological responses following traumatic brain injury in the rat | |
| US6022889A (en) | Pharmaceutical preparations containing bilobalide for the treatment of tension and anxiety | |
| Imbimbo et al. | A 6-month, double-blind, placebo-controlled trial of eptastigmine in Alzheimer’s disease | |
| US5182276A (en) | Nootropic agent | |
| JP2001507672A (ja) | Ｃｉｓ―縮合シクロペンテノ―１，２，４―トリオキサン誘導体を含有する抗マラリア組成物 | |
| KR102061482B1 (ko) | 섬유근육통 및 만성 피로 증후군을 치료하기 위한 (1r,4r)-6'-플루오로-(N-메틸- 또는 N,N-디메틸-)-4-페닐-4',9'-디하이드로-3'H-스피로-[사이클로헥산-1,1'-피라노[3,4,b]인돌]-4-아민 | |
| DE60305018T2 (de) | Citalopram zur behandlung von bluthochdruck | |
| RU2277096C2 (ru) | Средства против слабоумия, содержащие производное 2-арил-8-оксодигидропурина в качестве активного ингредиента | |
| Cohen et al. | Preliminary observations on use of frenquel in hospital psychiatry | |
| TWI313607B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| Cohen | The psychotomimetic agents | |
| Gallant | Antidepressant overdose: symptoms and treatment | |
| Maier et al. | The effect of ethanol treatment on social behavior in male rats | |
| CA2062094C (en) | Method of treating mania |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HMM4 | Cancellation of final prot. due to non-payment of fee |