Opioids and efflux transporters. Part 1: P-glycoprotein substrate activity of N-substituted analogs of meperidine.

ABSTRACT: P-Glycoprotein (P-gp) is an efflux transporter which is up-regulated at the blood-brain barrier in both morphine- and oxycodone-tolerant rats. Numerous studies have shown that many clinically employed opioid analgesics are substrates for 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 compounds, and show that a meperidine analog of greater potency, N-phenylbutyl-N-normeperidine, has low activity as a P-gp substrate and has the potential to be utilized as a tool to study the contribution of P-gp to the development of central tolerance to opioids.

SUBMITTER: Mercer SL 

PROVIDER: S-EPMC1850229 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature