摘要
为了观察对苯丙氨基苯乙酸（BPAA）对喹诺酮类药物与人γ-氨基丁酸A（GABAA）受体的相互作用，本研究首次用重组人类GABA受体，通过放射配体结合竞争抑制实验方法，依次进行了联苯丁酮酸、BPAA对萘啶酸类喹诺酮抗菌药依诺沙星（enoxaxine）竞争抑制3H一蝇蕈醇与Sf-9膜表达GABAA受体亚型A2β2γ2s、A2β3γ2s、α2β3γ2s、α3β3γ2s和α5β3γ2s结合的实验。结果发现BPAA能明显增加依诺沙星对3H-蝇曹醇与各受体亚型的竞争抑制作用，IC50减小104－105倍，与BPAA相比，联苯丁酮酸的抑制作用较小，IC50减小102倍。本研究直接反映了联苯丁酮酸和BPAA与喹诺酮类药物在体内与GABAA受体的相互作用，其作用机制可能是两种药物发生了化学／分子作用，形成一种与GABAA受体有着极高亲和力的新结构。目前，本研究还在继续进行，验证喹诺酮类药物和BPAA之间的这种化学／分子作用。
The co-administration of non-steroidal anti-inflammatory drug fenbufen increasesthe risk of epileptogenicity of quinolones significantly. In vitro 4-biphenylacetic acid, anactive metabolite of fenbufen, had been found to have the ability to increase the inhibitionof quinolones on the binding of 3H-muscimol or 3H-GABA and the GABAA receptor inanimal brain tissue. In this study, we observed the influence of fenbufen, BPAA on thecompetitive inhibitory effects of enoxacine, a new structure of quinolones, on the bindingof 3H-muscimol and the Sf-9 membrane expression GABA& receptor subtypes of humanbrain:A2β2γ2s、A2β3γ2s、α2β3γ2s、α3β3γ2s和α5β3γ2s with the radioligand binding assay (RLBA). Results showed that BPAA significantly increased thecompetitive inhibitory effect of enoxacine on the binding of 3H-muscimol and GABAAreceptor subtypes. The value of IC50 increased by 104~ 105. Fenbufen affected the binding of3H-muscimol and GABAA receptor subtypes only slightly. There was a parallel shift of thedose-response curve of the ligand to left. The study suggested that there may be an internalmolecular/chemistry interaction between quinolones and BPAA, producing a new structurewhich has a high affinity on the GABAA receptor sites. The research is continuing to testthe internal chemistry/molecular interaction between quinolones and BPAA.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2000年第3期191-194,共4页
The Chinese Journal of Clinical Pharmacology
