EFFECTS OF SOME EXCITATORY AMINO-ACID ANTAGONISTS AND DRUGS ENHANCINGGAMMA-AMINOBUTYRIC-ACID NEUROTRANSMISSION ON PEFLOXACIN-INDUCED SEIZURES IN DBA 2 MICE/

The behavioral and convulsant effects of pefloxacin (PEFLO), a quinolo ne derivative, were studied after intraperitoneal (i.p.) administratio n to Dilute Brown Agouti DBA/2J (DBA/2) mice, a strain genetically sus ceptible to sound-induced seizures. The anticonvulsant effects of some excitatory amino acid (EAA) antagonists acting at N-methyl-D-aspartat e (NMDA) or lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (A MPA) and kainate (KA) receptors and of some compounds enhancing gamma- aminobutyric acid (GABA)-ergic transmission against seizures induced b y PEFLO were also evaluated, The present study demonstrated that both groups of compounds administered i.p. or intracerebroventricularly wer e able to protect against seizures induced by PEFLO, However, ifenprod il and l)-4-[(4-fluorophenyl)methyl]-1-piperidine-ethanol (SL 82.0715) , two compounds acting on the polyamine site of the NMDA receptor comp lex, were unable to provide any protection. The relationship between t he different sites of action and the anticonvulsant activities of thes e derivatives were discussed, Although the main mechanism of PEFLO-ind uced seizures cannot be easily determined, potential interactions with the receptors of EAA exist. In fact, antagonists of EAA, and in parti cular, those acting at NMDA receptors, were able to increase the thres hold for the seizures or to prevent the seizures induced by PEFLO, whi le compounds acting at the polyamine site did not provide any protecti on. The AMPA-KA receptor antagonists were also able to exert anticonvu lsant 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.