Bidirectional effects of beta-carbolines in reflex epilepsy

Brain Res Bull. 1987 Sep;19(3):337-46. doi: 10.1016/0361-9230(87)90102-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Carbolines / adverse effects
  • Carbolines / therapeutic use*
  • Epilepsy / chemically induced
  • Epilepsy / drug therapy*
  • Female
  • Male
  • Mice
  • Mice, Inbred DBA
  • Papio
  • Valproic Acid / therapeutic use
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Anticonvulsants
  • Carbolines
  • methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate
  • gamma-Aminobutyric Acid
  • Valproic Acid
  • beta-carboline-3-carboxylic acid methyl ester