Comparative convulsant potencies of two 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 genetically susceptible to sound-induced seizure, and in C57 mice, a strain not prone to seizure. DBA/2 mice were more susceptible than C57 mice to seizures induced by imipenem-cilastatin or meropenem. Imipenem was also 1.9 times more potent than meropenem in inducing clonus in DBA/2 mice. To investigate the possibility that the seizure-inducing activity of imipenem might be due to a probenecid-like effect of cilastatin, animals were treated with imipenem alone. No significant differences were observed between imipenem-cilastatin and imipenem-treated animals. Thus, it is reasonable to exclude a probenecid-like effect of cilastatin. Although the main mechanism for seizure-like activity of imipenem cannot be easily determined, we believe that several mechanisms may 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 imipenem, showed weak or no convulsant effects.