Opioids and efflux transporters. Part 3: P-glycoprotein substrate activity of 3-hydroxyl addition to meperidine analogs

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:18

Article

Mercer, Susan L.¹  Cunningham, Christopher W.¹  Eddington, Natalie D.¹  Coop, Andrew¹ 

[1] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA

关键词: meperidine;    P-glycoprotein;    opioids;    tolerance;   

DOI  :  10.1016/j.bmcl.2008.04.046

来源: Elsevier

【 摘 要 】

Numerous studies have shown that many clinically employed opioid analgesics are substrates for P-glycoprotein (P-gp), suggesting that up-regulation of P-gp may contribute to the development of central tolerance to opioids. The studies herein focus on the development of SAR for P-gp substrate activity in the meperidine series of opioids. Addition of a 3-OH to meperidine and the ketone analog of meperidine yielding bemidone and ketobemidone, respectively, significantly increased P-gp substrate affinity. The results of this study have implications in the development of novel analgesics to be utilized as tools to study the contribution of P-gp on the development of central tolerance to opioids. (C) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

Free