De Sarro G, Renne S, Nava F, De Sarro A
Department of Experimental and Clinical Medicine, Faculty of Medicine, Catanzaro, Italy.
J Pharm Pharmacol. 1994 Dec;46(12):1017-22. doi: 10.1111/j.2042-7158.1994.tb03259.x.
The anticonvulsant activity of 3-((+/-)-2-carboxypiperazin-4-yl)-1-propenyl-1-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 (20 mg kg-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.
研究了两种兴奋性氨基酸拮抗剂3-((±)-2-羧基哌嗪-4-基)-1-丙烯基-1-膦酸（CPPene）和2,3-二羟基-6-硝基-7-氨磺酰基-苯并(F)喹喔啉（NBQX）腹腔注射（i.p.）或脑室内注射（i.c.v.）后对DBA/2小鼠听源性惊厥的抗惊厥活性。NBQX给药后15 - 30分钟以及CPPene给药后45 - 180分钟观察到最大抗惊厥保护作用。与非甾体抗炎药芬布芬（20 mg kg-1，i.p.）共同给药，增强并延长了CPPene和NBQX的抗惊厥作用，同时也增强并延长了对转棒性能的损害。抗惊厥活性的增强以及转棒性能损害的延长表明，芬布芬可能与CPPene和NBQX存在一些药代动力学相互作用，并且芬布芬能够提高这些兴奋性氨基酸拮抗剂的脑内水平。特别是，芬布芬对NBQX作用的增强程度大于对CPPene的增强程度，这表明这些兴奋性氨基酸拮抗剂的化学结构导致了CPPene或NBQX与芬布芬之间不同程度的相互作用。NBQX似乎与喹诺酮类有显著相似性，而CPPene则不然。此外，芬布芬可能从血浆结合位点置换CPPene和NBQX或抑制其肾脏排泄。目前的数据也与先前关于芬布芬和喹诺酮类药代动力学相互作用的研究一致。
