DE69424009T2 - Verwendung von (S)-(-)-alpha-ethyl-2-oxo-1-pyrrolidinacetamid zur Herstellung eines Medikaments zur Behandlung von Angst - Google Patents
Verwendung von (S)-(-)-alpha-ethyl-2-oxo-1-pyrrolidinacetamid zur Herstellung eines Medikaments zur Behandlung von AngstInfo
- Publication number
- DE69424009T2 DE69424009T2 DE69424009T DE69424009T DE69424009T2 DE 69424009 T2 DE69424009 T2 DE 69424009T2 DE 69424009 T DE69424009 T DE 69424009T DE 69424009 T DE69424009 T DE 69424009T DE 69424009 T2 DE69424009 T2 DE 69424009T2
- Authority
- DE
- Germany
- Prior art keywords
- anxiety
- oxo
- ethyl
- test
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 208000019901 Anxiety disease Diseases 0.000 title claims abstract description 45
- HPHUVLMMVZITSG-LURJTMIESA-N levetiracetam Chemical compound CC[C@@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-LURJTMIESA-N 0.000 title claims abstract description 32
- 239000003814 drug Substances 0.000 title claims abstract description 19
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 230000036506 anxiety Effects 0.000 title abstract description 28
- 150000001875 compounds Chemical class 0.000 claims description 55
- 229940049706 benzodiazepine Drugs 0.000 claims description 16
- 150000001557 benzodiazepines Chemical class 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 description 68
- 238000012360 testing method Methods 0.000 description 46
- 230000000949 anxiolytic effect Effects 0.000 description 30
- 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 24
- 229960004782 chlordiazepoxide Drugs 0.000 description 24
- 239000002249 anxiolytic agent Substances 0.000 description 21
- 230000000694 effects Effects 0.000 description 18
- 238000000034 method Methods 0.000 description 17
- 230000004044 response Effects 0.000 description 16
- 230000035882 stress Effects 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- 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 9
- 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 9
- 239000000203 mixture Substances 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000006399 behavior Effects 0.000 description 8
- 230000024188 startle response Effects 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 7
- 230000001575 pathological effect Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 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 6
- 229960003529 diazepam Drugs 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 238000000585 Mann–Whitney U test Methods 0.000 description 5
- GMZVRMREEHBGGF-UHFFFAOYSA-N Piracetam Chemical class NC(=O)CN1CCCC1=O GMZVRMREEHBGGF-UHFFFAOYSA-N 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 230000002887 neurotoxic effect Effects 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 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 4
- 230000008901 benefit Effects 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 229960004526 piracetam Drugs 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 206010021118 Hypotonia Diseases 0.000 description 3
- 238000011785 NMRI mouse Methods 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 230000036640 muscle relaxation Effects 0.000 description 3
- 230000036515 potency Effects 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 238000010825 rotarod performance test Methods 0.000 description 3
- 238000012453 sprague-dawley rat model Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 206010029350 Neurotoxicity Diseases 0.000 description 2
- 206010029897 Obsessive thoughts Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 206010039897 Sedation Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 208000007271 Substance Withdrawal Syndrome 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
- 239000004480 active ingredient Substances 0.000 description 2
- 230000008649 adaptation response Effects 0.000 description 2
- 229940005530 anxiolytics Drugs 0.000 description 2
- 230000003542 behavioural effect 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
- 229940125904 compound 1 Drugs 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000002996 emotional effect Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 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
- 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
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000036280 sedation Effects 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 229940037128 systemic glucocorticoids Drugs 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- 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
- 208000008811 Agoraphobia Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000031091 Amnestic disease Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 208000024255 Audiogenic seizures Diseases 0.000 description 1
- 206010063659 Aversion Diseases 0.000 description 1
- 206010013142 Disinhibition Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 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
- 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
- 208000001953 Hypotension 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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 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
- 206010033664 Panic attack 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
- 206010041349 Somnolence Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010042008 Stereotypy 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
- 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
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000006978 adaptation 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
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000013459 approach Methods 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
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000009286 beneficial effect Effects 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
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 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
- 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
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000006949 cholinergic function Effects 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 229940014259 gelatin Drugs 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
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000036541 health Effects 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
- 230000036543 hypotension Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 208000018879 impaired coordination Diseases 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 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
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 230000009907 neuroendocrine response Effects 0.000 description 1
- 230000003040 nociceptive effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 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
- 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
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 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
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 230000028527 righting reflex 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
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000008925 spontaneous activity Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 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
- 230000009182 swimming Effects 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
- 239000003826 tablet Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 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)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Anesthesiology (AREA)
- Psychiatry (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 |
|---|---|
| DE69424009D1 DE69424009D1 (de) | 2000-05-25 |
| DE69424009T2 true DE69424009T2 (de) | 2000-09-14 |
Family
ID=10742476
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69424009T Expired - Lifetime DE69424009T2 (de) | 1993-09-24 | 1994-09-21 | Verwendung von (S)-(-)-alpha-ethyl-2-oxo-1-pyrrolidinacetamid zur Herstellung eines Medikaments zur Behandlung von Angst |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US5447952A (enExample) |
| EP (1) | EP0645139B1 (enExample) |
| JP (1) | JP3688735B2 (enExample) |
| KR (1) | KR950007848A (enExample) |
| AT (1) | ATE191849T1 (enExample) |
| AU (1) | AU672334B2 (enExample) |
| CA (1) | CA2132509A1 (enExample) |
| DE (1) | DE69424009T2 (enExample) |
| ES (1) | ES2145818T3 (enExample) |
| GB (1) | GB9319732D0 (enExample) |
| HU (1) | HU217124B (enExample) |
| NO (1) | NO943521L (enExample) |
| NZ (1) | NZ264506A (enExample) |
| RU (1) | RU2142274C1 (enExample) |
| SG (1) | SG86284A1 (enExample) |
| TW (1) | TW283642B (enExample) |
| ZA (1) | ZA947444B (enExample) |
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 |
| EE200200274A (et) | 1999-12-01 | 2003-06-16 | Ucb, S.A. | Pürrolidiinatseetamiidi derivaadi kasutamine ravimi valmistamiseks, mis on ette nähtud kesknärvisüsteemi häirete ravimiseks, ja farmatseutiline kompositsioon |
| 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 |
| CN101400348A (zh) * | 2006-03-15 | 2009-04-01 | 埃科特莱茵药品有限公司 | 用于提高记忆功能的四氢异喹啉衍生物 |
| EP2051696A2 (en) * | 2006-08-18 | 2009-04-29 | Morton Grove Pharmaceuticals, Inc. | Stable liquid levetiracetam compositions and methods |
| WO2009004584A1 (en) * | 2007-07-03 | 2009-01-08 | Actelion Pharmaceuticals Ltd | 3-aza-bicyclo[3.3.0]octane compounds |
| RU2478099C2 (ru) * | 2007-07-27 | 2013-03-27 | Актелион Фармасьютиклз Лтд | Производные 2-аза-бицикло[3.3.0]октана |
| DK3260118T3 (da) * | 2008-10-16 | 2021-04-19 | Univ Johns Hopkins | Fremgangsmåder og sammensætninger til forbedring af kognitiv funktion |
| US8191547B2 (en) * | 2008-10-23 | 2012-06-05 | S-2Tech Llc | Portable solar-heating system having an inflatable solar collector |
| US20100159009A1 (en) * | 2008-12-24 | 2010-06-24 | Zhongshui Yu | Controlled-release formulations |
| US20100172979A1 (en) * | 2008-12-24 | 2010-07-08 | Zhongshui Yu | Controlled-release formulations |
| CN102905532A (zh) * | 2010-02-09 | 2013-01-30 | 约翰斯.霍普金斯大学 | 用于改善认知功能的方法和组合物 |
| CN103476255A (zh) * | 2011-02-09 | 2013-12-25 | 约翰斯霍普金斯大学 | 用于改善认知功能的方法和组合物 |
| EP3610890A1 (en) | 2012-11-14 | 2020-02-19 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| US10806717B2 (en) | 2013-03-15 | 2020-10-20 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| AU2014228512A1 (en) | 2013-03-15 | 2015-10-01 | Agenebio, Inc. | Methods and compositions for improving cognitive function |
| US10925834B2 (en) | 2015-05-22 | 2021-02-23 | Agenebio, Inc. | Extended release pharmaceutical compositions of levetiracetam |
| US20220047548A1 (en) * | 2018-12-04 | 2022-02-17 | Metys Pharmaceuticals AG | SYNERGISTIC COMPOSITIONS COMPRISING (R)-2-(2-OXOPYRROLIDIN-1-YL)BUTANAMIDE AND (S)-2-(2-e OXOPYRROLEDIN-1-YL)BUTANAMEDE IN A NON-RACEMIC RATIO |
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 CA CA002132509A patent/CA2132509A1/en not_active Abandoned
- 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
- 1994-09-21 SG SG9502212A patent/SG86284A1/en unknown
- 1994-09-21 EP EP94870152A patent/EP0645139B1/fr 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 DE DE69424009T patent/DE69424009T2/de not_active Expired - Lifetime
- 1994-09-21 TW TW083108691A patent/TW283642B/zh active
- 1994-09-21 ES ES94870152T patent/ES2145818T3/es not_active Expired - Lifetime
- 1994-09-22 AU AU74169/94A patent/AU672334B2/en not_active Ceased
- 1994-09-22 JP JP22833194A patent/JP3688735B2/ja not_active Expired - Fee Related
- 1994-09-22 NO NO943521A patent/NO943521L/no unknown
- 1994-09-23 KR KR1019940024170A patent/KR950007848A/ko not_active Abandoned
- 1994-09-23 RU RU94034109A patent/RU2142274C1/ru active
- 1994-09-23 ZA ZA947444A patent/ZA947444B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA947444B (en) | 1995-05-11 |
| CA2132509A1 (en) | 1995-03-25 |
| DE69424009D1 (de) | 2000-05-25 |
| SG86284A1 (en) | 2002-02-19 |
| NZ264506A (en) | 1997-09-22 |
| AU7416994A (en) | 1995-04-06 |
| US5447952A (en) | 1995-09-05 |
| ATE191849T1 (de) | 2000-05-15 |
| AU672334B2 (en) | 1996-09-26 |
| EP0645139A1 (fr) | 1995-03-29 |
| ES2145818T3 (es) | 2000-07-16 |
| KR950007848A (ko) | 1995-04-15 |
| EP0645139B1 (fr) | 2000-04-19 |
| JP3688735B2 (ja) | 2005-08-31 |
| HU217124B (hu) | 1999-11-29 |
| NO943521D0 (no) | 1994-09-22 |
| NO943521L (no) | 1995-03-27 |
| GB9319732D0 (en) | 1993-11-10 |
| TW283642B (enExample) | 1996-08-21 |
| HUT68299A (en) | 1995-06-28 |
| RU2142274C1 (ru) | 1999-12-10 |
| JPH07149639A (ja) | 1995-06-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69424009T2 (de) | Verwendung von (S)-(-)-alpha-ethyl-2-oxo-1-pyrrolidinacetamid zur Herstellung eines Medikaments zur Behandlung von Angst | |
| DE60034815T2 (de) | Ein pyrrolidinacetatderivat zur behandlung von chronischem oder neuropathischem schmerz | |
| DE69636308T2 (de) | Tumornekrosefaktor alpha (tnf-alpha) hemmende arzneistoffe | |
| DE69233648T2 (de) | Verwendung von Galanthaminen zur Linderung von Benzodiazepin-Nebenwirkungen | |
| CH647150A5 (de) | Zubereitung, enthaltend ein tranquillans und ein propiophenon. | |
| DE69731968T2 (de) | Isovaleramid zur behandlung von schüttelkrämpfen, epilepsie, kopfschmerzen und spastischer lähmung | |
| DE3390116C2 (de) | Verbesserte, Koffein enthaltende, analgetische und antiinflammatorische Mittel | |
| DE3343934A1 (de) | M-chlor-(alpha)-tert.-butylaminopropiophenon und seine verwendung zur senkung des cholesterolspiegels | |
| CH670952A5 (enExample) | ||
| DE60206280T2 (de) | Verwendung von extrakten aus ginkgo biloba zur herstellung eines medikaments zur behandlung von sarcopenia | |
| EP1152762A1 (de) | Verwendung von desoxypeganin zur behandlung von alzheimerischer demenz | |
| DE68911273T2 (de) | Benzothiazepine zur Herstellung von Medikamenten zur Milderung von epileptischen Anfällen. | |
| DE69725613T2 (de) | Neue therapeutische verwendung eines thienylcyclohexylaminderivates | |
| JPH06128165A (ja) | 脳機能改善剤 | |
| DE60318453T2 (de) | Analgetikum für neugeborene und föten | |
| DE2720194A1 (de) | Verwendung von trazodon und etoperidon zum behandeln des parkinson-tremors und anderer extra- pyramidaler syndrome | |
| DE69710526T2 (de) | Verwendung von 3-(4-Hexyloxy-1,2,5-Thiadiazol-3-yl)-1,2,5,6-Tetrahydro-1-Methylpyridin (Xanomelin) zur Behandlung von bipolaren Störungen | |
| DE69904206T2 (de) | Verwendung von cetirizin zur vorbeugung von asthma eintritt | |
| DD297557A5 (de) | Verwendung von dopamin-autorezeptor-agonisten bei der behandlung von drogenabhaengigkeit | |
| DE60318916T2 (de) | Ein verfahren zum screening von neuroaktiven substanzen und die assoziierte neutrale plastizität | |
| EP0604830B1 (de) | Verwendung mindestens eines Paf-Antagonisten zur Herstellung eines Arzneimittels zur Behandlung oder Vorbeugung des Hyperinsulinismus | |
| DE69424779T2 (de) | Verwendung von triazinverbindungen bei angstzuständen | |
| DE69218544T2 (de) | Verwendung von BMY 14802 zur Behandlung von Angstzuständen bei Patienten mit Benzodiazepin-Entzugserscheinungen | |
| DE60214987T2 (de) | Mittel gegen posttraumatische stresszustände | |
| EP0398171A2 (de) | Verwendung von Imidazodiazepinen bei der Behandlung von neurologischen Symptomen, welche mit zirkulatorischen Störungen des Gehirns assoziiert sind |