Abstract |
Derivatives of ethyl-beta-carboline-3-carboxylate, ZK 91296, ZK 93423 and ZK 95962 have potent anticonvulsant activity against sound-induced seizures in audiogenic DBA/2 mice and against photically-induced seizures in the baboon, Papio papio. The convulsant beta-carbolines, DMCM and beta-CCM, have proconvulsant and convulsant activity in the same animal models. DMCM and beta-CCM are similar in potency as convulsants in DBA/2 mice (ED50 value for DMCM: 1.3 mg/kg; ED50 value for beta-CCM; 0.8 mg/kg), but differ with respect to their profiles for protection by anticonvulsant drugs. The anticonvulsant potencies of diazepam and clobazam are similar against both types of beta-carboline-induced seizures, whereas quazepam protects better against beta-CCM seizures (4 fold elevation in ED50 value at 1 mg/kg quazepam IP) than against DMCM seizures (1.7 fold elevation in ED50 value), supporting a preferential action of beta-CCM on BZ1 receptors. Valproate (400 mg/kg) and gamma-vinyl-GABA (1.5 g/kg) protect better against beta-CCM seizures (9.5 and 5.9 fold elevations in ED50 values respectively) than against DMCM seizures (1.8 and 2.7 fold elevations in ED50 values respectively). The excitatory amino acid antagonist, 2-amino-7-phosphonoheptanoic acid, has significant anticonvulsant activity against DMCM seizures. The elevated regional GABA levels in brains of DBA/2 mice observed during beta-CCM seizures are eliminated by the pretreatment with Ro 15-1788, which also blocks the seizure activity.
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Authors | A G Chapman, G B De Sarro, M Premachandra, B S Meldrum |
Journal | Brain research bulletin
(Brain Res Bull)
Vol. 19
Issue 3
Pg. 337-46
(Sep 1987)
ISSN: 0361-9230 [Print] United States |
PMID | 3119161
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anticonvulsants
- Carbolines
- methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate
- gamma-Aminobutyric Acid
- Valproic Acid
- beta-carboline-3-carboxylic acid methyl ester
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Topics |
- Animals
- Anticonvulsants
(adverse effects, therapeutic use)
- Brain
(drug effects, metabolism, physiopathology)
- Carbolines
(adverse effects, therapeutic use)
- Epilepsy
(chemically induced, drug therapy)
- Female
- Male
- Mice
- Mice, Inbred DBA
- Papio
- Valproic Acid
(therapeutic use)
- gamma-Aminobutyric Acid
(metabolism)
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