{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mercer SL"],"funding":["NIDA NIH HHS"],"pagination":["1160-2"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC1850229"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(5)"],"pubmed_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."],"journal":["Bioorganic & medicinal chemistry letters"],"pubmed_title":["Opioids and efflux transporters. Part 1: P-glycoprotein substrate activity of N-substituted analogs of meperidine."],"pmcid":["PMC1850229"],"funding_grant_id":["K02 DA019634","R01 DA013583","DA-13583"],"pubmed_authors":["Hassan HE","Cunningham CW","Mercer SL","Coop A","Eddington ND"],"additional_accession":[]},"is_claimable":false,"name":"Opioids and efflux transporters. Part 1: P-glycoprotein substrate activity of N-substituted analogs of meperidine.","description":"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.","dates":{"release":"2007-01-01T00:00:00Z","publication":"2007 Mar","modification":"2020-10-29T12:41:06Z","creation":"2019-03-27T02:03:43Z"},"accession":"S-EPMC1850229","cross_references":{"pubmed":["17251015"],"doi":["10.1016/j.bmcl.2006.12.042"]}}