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Vol. 297, Issue 2, 688-695, May 2001
Department of Pharmacology, Temple University Medical School,
Philadelphia, Pennsylvania
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-(
-thio)triphosphate
([35S]GTPS) 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]GTPS binding. NorBUP
exhibited high affinities for µ-, 
-, and 
-opioid receptors with
Ki values in the nanomolar or subnanomolar range, comparable to those of BUP. NorBUP and BUP had low affinities for the ORL1 receptor with Ki values in the
micromolar range. In the [35S]GTPS binding assay,
norBUP displayed characteristics distinct from BUP. At the
-receptor, norBUP was a potent full agonist, yet BUP had no agonist
activity and antagonized actions of norBUP and DPDPE. At µ- and
-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.
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