P-糖蛋白与中枢抑制药物相互作用的体外研究

In vitro study on the interactions of P-gp and central depressants

目的:基于"上调MDR(multiple drug resistance)基因、诱导P-糖蛋白(P-gp,P-glycoprotein)外向转运解除中枢抑制药物中毒"的机制研究,对临床中毒多发的中枢抑制药物建立P-gp底物谱,明确适合该解救治疗方案的药物(毒物)。方法:采用三磷酸腺苷酶(adenosine triphosphate,ATP)酶活性测试法确定待测中枢抑制药物是否为P-gp的底物。结果:舒必利、齐拉西酮、佐匹克隆、氯米帕明、西酞普兰及吗氯贝胺均为P-gp底物。舒必利、齐拉西酮与西酞普兰为非浓度依赖的ATP酶抑制剂,佐匹克隆、氯米帕明与吗氯贝胺浓度依赖的ATP酶双向调节子。结论:该研究结果将为新的中枢药物中毒解救方案的临床应用提供参考和依据。

OBJECTIVE Based on new detoxication mechanism rescuing for central depressants detoxification through induc- tion P-gp transportation by up-regulate MDR1 gene, it is necessary to establish P-gp substrates spectrum to match the novel method. METHODS By using ATPase activity assay to identify whether the six central depressants were P-gp substrates. RF_~ULTS Sulpiride, ziprasidone, zopie[one, clomipramine,citalopram and moclohemide were all P-gp substrates, sulpiride, ziprasidone and citalopram were non-concentration dependent ATPase inhibitors, zopiclone, clomipramine and moclobemide were concentration-dependent bidirection regulators of ATPase. CONCLUSION The results of this study provide references and basis for clinical application of the new detoxication treatment of central depressants.