Effects of some excitatory amino acid antagonists and drugs enhancing gamma-aminobutyric acid neurotransmission on pefloxacin-induced seizures in DBA/2 mice.

The behavioral and convulsant effects of pefloxacin (PEFLO), a quinolone derivative, were studied after intraperitoneal (i.p.) administration to Dilute Brown Agouti DBA/2J (DBA/2) mice, a strain genetically susceptible to sound-induced seizures. The anticonvulsant effects of some excitatory amino acid (EAA) antagonists acting at N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptors and of some compounds enhancing gamma-aminobutyric acid (GABA)-ergic transmission against seizures induced by PEFLO were also evaluated. The present study demonstrated that both groups of compounds administered i.p. or intracerebroventricularly were able to protect against seizures induced by PEFLO. However, ifenprodil and (+/-)-alpha-(chlorophenyl)-4-[(4-fluorophenyl)methyl]-1-piperidine-ethan ol (SL 82.0715), two compounds acting on the polyamine site of the NMDA receptor complex, were unable to provide any protection. The relationship between the different sites of action and the anticonvulsant activities of these derivatives were discussed. Although the main mechanisms of PEFLO-induced seizures cannot be easily determined, potential interactions with the receptors of EAA exist. In fact, antagonists of EAA, and in particular, those acting at NMDA receptors, were able to increase the threshold for the seizures or to prevent the seizures induced by PEFLO, while compounds acting at the polyamine site did not provide any protection. The AMPA-KA receptor antagonists were also able to exert anticonvulsant activity, but with minor potency in comparison to those of NMDA antagonists. In addition, the fact that compounds enhancing GABA-ergic neurotransmission were also able to protect the mice against seizures induced by PEFLO suggests an involvement of GABA system.