title: Structural determinants of opioid and NOP receptor activity in derivatives of buprenorphine.
abstract: The unique pharmacological profile of buprenorphine has led to its considerable success as an analgesic and as a treatment agent for drug abuse. Activation of nociceptin/orphanin FQ peptide (NOP) receptors has been postulated to account for certain aspects of buprenorphine's behavioral profile. In order to investigate the role of NOP activation further, a series of buprenorphine analogues has been synthesized with the aim of increasing affinity for the NOP receptor. Binding and functional assay data on these new compounds indicate that the area around C20 in the orvinols is key to NOP receptor activity, with several compounds displaying higher affinity than buprenorphine. One compound, 1b, was found to be a mu opioid receptor partial agonist of comparable efficacy to buprenorphine but with higher efficacy at NOP receptors.
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, U.K.
authors.forename: Gerta
authors.initials: G
authors.lastname: Cami-Kobeci
authors.forename: Willma E
authors.initials: WE
authors.lastname: Polgar
authors.forename: Taline V
authors.initials: TV
authors.lastname: Khroyan
authors.forename: Lawrence
authors.initials: L
authors.lastname: Toll
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Husbands
mesh_terms: D000818:Animals; D002047:Buprenorphine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D054333:Drug Partial Agonism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
chemical_list: D008024:Ligands; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D002047:Buprenorphine; D000094942:Nociceptin Receptor