Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist

J Pharmacol Exp Ther. 2001 May;297(2):688-95.


Buprenorphine (BUP) is an oripavine analgesic that is beneficial in the maintenance treatment of opiate-dependent individuals. Although BUP has been studied extensively, relatively little is known about norbuprenorphine (norBUP), a major dealkylated metabolite of BUP. We now describe the binding of norBUP to opioid and nociceptin/orphanin FQ (ORL1) receptors, and its effects on [(35)S]guanosine-5'-O-(gamma-thio)triphosphate ([(35)S]GTP gamma S) binding mediated by opioid or ORL1 receptors and in the mouse acetic acid writhing test. Chinese hamster ovary cells stably transfected with each receptor were used for receptor binding and [(35)S]GTP gamma S binding. NorBUP exhibited high affinities for mu-, delta-, and kappa-opioid receptors with K(i) values in the nanomolar or subnanomolar range, comparable to those of BUP. NorBUP and BUP had low affinities for the ORL1 receptor with K(i) values in the micromolar range. In the [(35)S]GTP gamma S binding assay, norBUP displayed characteristics distinct from BUP. At the delta-receptor, norBUP was a potent full agonist, yet BUP had no agonist activity and antagonized actions of norBUP and DPDPE. At mu- and kappa-receptors, both norBUP and BUP were potent partial agonists, with norBUP having moderate efficacy and BUP having low efficacy. At the ORL1 receptor, norBUP was a full agonist with low potency, while BUP was a potent partial agonist. In the writhing test, BUP and norBUP both suppressed writhing in an efficacious and dose-dependent manner, giving A(50) values of 0.067 and 0.21 mg/kg, s.c., respectively. These results highlight the similarities and differences between BUP and norBUP, each of which may influence the unique pharmacological profile of BUP.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetic Acid
  • Adenylyl Cyclase Inhibitors
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Buprenorphine / analogs & derivatives
  • Buprenorphine / pharmacology*
  • CHO Cells
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Colforsin / pharmacology
  • Cricetinae
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Mice
  • Narcotic Antagonists
  • Nociceptin Receptor
  • Pain Measurement / drug effects
  • Receptors, Opioid / agonists*
  • Receptors, Opioid / biosynthesis


  • Adenylyl Cyclase Inhibitors
  • Analgesics, Opioid
  • Narcotic Antagonists
  • Receptors, Opioid
  • Colforsin
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Buprenorphine
  • norbuprenorphine
  • Acetic Acid
  • Nociceptin Receptor