PT  - JOURNAL ARTICLE
AU  - Huang, Peng
AU  - Kehner, George B.
AU  - Cowan, Alan
AU  - Liu-Chen, Lee-Yuan
TI  - Comparison of Pharmacological Activities of Buprenorphine and Norbuprenorphine: Norbuprenorphine Is a Potent Opioid Agonist
DP  - 2001 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 688--695
VI  - 297
IP  - 2
4099  - http://jpet.aspetjournals.org/content/297/2/688.short
4100  - http://jpet.aspetjournals.org/content/297/2/688.full
SO  - J Pharmacol Exp Ther2001 May 01; 297
AB  - 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 [35S]guanosine-5′-O-(γ-thio)triphosphate ([35S]GTPγS) 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 [35S]GTPγS binding. NorBUP exhibited high affinities for μ-, δ-, and κ-opioid receptors withK 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 [35S]GTPγS binding assay, norBUP displayed characteristics distinct from BUP. At the δ-receptor, norBUP was a potent full agonist, yet BUP had no agonist activity and antagonized actions of norBUP and DPDPE. At μ- and κ-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 A50 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. The American Society for Pharmacology and Experimental Therapeutics