title: Pharmacological characterization of buprenorphine, a mixed agonist-antagonist with kappa 3 analgesia.
abstract: Buprenorphine is a mixed opioid agonist/antagonist analgesic. This study was designed to determine the role of opioid receptor subtypes, especially kappa 3, in buprenorphine-induced analgesia in mice. Buprenorphine, when injected systemically, revealed a potent analgesic effect by tailflick assay, with a biphasic dose-response curve, which was reversed by naloxone. The presence of analgesic cross-tolerance between buprenorphine and naloxone benzoylhydrazone (NalBzoH) and morphine indicated a role for kappa 3 and mu receptor subtype in buprenorphine analgesia. Additional studies with selective opioid antagonists indicated kappa 1 mechanisms of action. We did not detect any involvement of the delta receptor subtype. Low doses of buprenorphine antagonized morphine analgesia, while high doses of buprenorphine coadministered with morphine elicited increasing analgesia in a dose-dependent manner. These findings suggest that buprenorphine elicits analgesia through an interaction with kappa 3 receptors and to a lesser extent with kappa 1 as well as its activity as partial mu receptor agonist.
authors.affiliation: Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel. anat03@ccsg.tau.ac.il
authors.forename: C G
authors.initials: CG
authors.lastname: Pick
authors.forename: Y
authors.initials: Y
authors.lastname: Peter
authors.forename: S
authors.initials: S
authors.lastname: Schreiber
authors.forename: R
authors.initials: R
authors.lastname: Weizman
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D004347:Drug Interactions; D004361:Drug Tolerance; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012680:Sensitivity and Specificity
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D004745:Enkephalins; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; C058380:naloxone benzoylhydrazone; D009270:Naloxone; D002047:Buprenorphine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-