Fenbufen Pretreatment Potentiates the Anticonvulsant Activity of CPPene and NBQX in DBA/2 Mice

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Abstract
— The anticonvulsant activity of 3‐((±)‐2‐carboxypiperazin‐4‐yl)‐***l‐propenyl‐***l‐phosphonic acid (CPPene) and 2,3‐dihydroxy‐6‐nitro‐7‐sulphamoyl‐benzo(F)quinoxoline (NBQX), two excitatory amino acid antagonists, was studied against audiogenic seizures in DBA/2 mice, following intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration. Maximal anticonvulsant protection was observed 15–30 min following NBQX and 45–180 min after CPPene. Coadministration with fenbufen (20mgkg‐1, i.p.), a non‐steroidal anti‐inflammatory agent, enhanced and prolonged the anticonvulsant actions of CPPene and NBQX and also potentiated and prolonged the impairment of rotarod performance. The enhancement of the anticonvulsant activity and the prolonged impairment of rotarod performance suggests that fenbufen may have some pharmacokinetic interactions with CPPene and NBQX and that fenbufen is able to increase the brain levels of these excitatory amino acid antagonists. In particular, fenbufen was able to exert a major degree of potentiation of effects of NBQX rather than those of CPPene, suggesting that the chemical structures of these excitatory amino acid antagonists are responsible for the different degree of interactions between CPPene or NBQX and fenbufen. NBQX appears to have a notable similarity with quinolones whilst CPPene does not. Additionally fenbufen may displace CPPene and NBQX from plasma binding sites or inhibit the renal excretion. The present data are also consistent with previous studies showing pharmacokinetic interactions between fenbufen and quinolones.