GABA系作動薬のElマウスけいれん及び脳内アミノ酸に及ぼす影響に関する研究

It is known that GABA is one of the important inhibitory chemical neurotransmitter substances in the central nervous system. Some neurochemical disorders, such as epileptic seizures, have been treated by reinforcement of the GABAergic transmission system. Recently we have studied the action of various GABA receptor modulators on induced seizures in El mice. An intraperitoneal injection of γ-vinyl GABA (a GABA transaminase blocker), 1500 mg/kg, completely inhibited El mouse seizures with significatly increased endogeneous GABA levels in the brain. Administration of 3 mg/kg of muscimol (a GABA agonist), i.p., completely inhibited the seizures with increased glutamine levels in the brain. Administration of 100 mg/kg of progabide (a GABA agonist), i.p., completely inhibited the seizures with no significant chnage in amino acids in the brain. An intraperitoneal injection of 32 mg/kg of diazepam completely inhibited the seizures with significantly increased glutamine levels in the brain. An intraperitoneal injection of 20 mg/kg of baclofen (an agonist for the GABA receptor) blocked the seizures with decreased levels of GABA, glutamic acid and alanine in the brain. These results suggest that inhibition of E1 mouse seizures may depend on an increased GABA level in the case of γ-vinyl GABA, on the action of a GABA receptor agonist in the case of muscimol and progabide, on the reinforcement of GABA receptor binding through benzodiazepine receptor in the case of diazepam, and on the action of a GABA(B) receptor agonist in the case of baclofen.