COMPARATIVE CONVULSANT POTENCIES OF 2 CARBAPENEM DERIVATIVES IN C57 AND DBA 2 MICE/

The behavioural and convulsant effects of imipenem and meropenem were studied after intraperitoneal administration in DBA/2 mice, a strain g enetically susceptible to sound-induced seizure, and in C57 mice, a st rain not prone to seizure. DBA/2 mice were more susceptible than C57 m ice to seizures induced by imipenem-cilastatin or meropenem. Imipenem was also 1.9 times more potent than meropenem in inducing clonus in DB A/2 mice. To investigate the possibility that the seizure-inducing act ivity of imipenem might be due to a probenecid-like effect of cilastat in, animals were treated with imipenem alone. No significant differenc es were observed between imipenem-cilastatin and imipenem-treated anim als. Thus, it is reasonable to exclude a probenecid-like effect of cil astatin. Although the main mechanism for seizure-like activity of imip enem cannot be easily determined, we believe that several mechanisms m ay be involved. An increased excitation of the central nervous system (CNS) by inhibition of GABA binding to receptors and a slow clearance of imipenem from the CNS may be postulated. Cilastatin did not induce seizures. In addition, meropenem, a compound structurally related to i mipenem, showed weak or no convulsant effects.