Epileptogenic action of penicillin derivatives: structure-activity relationship

In the hippocampal slice preparation, perfusion with benzyl penicillin evokes multiple population spikes and spontaneous discharges. Doses of 0.25 to 2 mM of the drug produced this effect within 20-40 min. Cleavage products and analogues of benzyl penicillin, penicilloic acid, 6-aminopenicillanic acid, cephalexin, thioproline and penicillamine, were devoid of such action. It is concluded that the structural requirements for epileptogenic action of penicillin include not only the beta-lactam ring and side chain substitution on C-6, but also the thiazolidine ring.