Relation between convulsant activity of biapenem, a new carbapenem, and its binding affinity to GABA receptor

Abstract

Beta-lactams have been well known to have convulsant activity. Specially imipemen, the first carbapenem introduced in the clinical field, have been reported to induce convulsions. We have demonstrated that cephalosporins inhibited the receptor binding of γ-aminobutyric acid (GABA), an inhibitory transmitter in the central nervous system, and we suggest that the inhibition of GABA receptor binding might be responsible for the onset of the convulsions induced by these agents. Then, we studied the convulsant activity of BIPM, a new carbapenem, and its effect on GABA receptor binding. Intraventricular injection of imipenem, panipenem and cefazolin induced convulsions in a dose-dependent manner in mice, and their ED₅₀ values were 13, 25, 17nmol, respectively. On the other hand, BIPM induced convulsions in 40% of mice at its high dose (200nmol). Imipenem, panipenem, cefazolin and BIPM inhibited GABA receptor binding in a concentration-dependent manner, and their IC₅₀ values were 1.1, 0.41, 1.7 and 7.1mM, respectively. These in vivo and in vitro results suggest that the inhibition of GABA receptor binding might be responsible for the onset of the convulsions induced by these agents and that BIPM might have weaker convulsant activity than other 3 referenced agents.