title: Buprenorphine is an Antagonist at the ϰ Opioid Receptor.
abstract: The effect of buprenorphine on bremazocine-induced diuresis was tested in the rat to determine the nature of buprenorphine's action at the ϰ opioid receptor. Both morphine-tolerant and naive rats were used to account for possible antidiuretic effects of buprenorphine at the µ site. Separate experiments established that the morphine pretreatment caused profound tolerance with respect to the antidiuretic action of µ agonists. Buprenorphine acted as a potent antagonist (ID50 = 11µg/kg) of the diuretic action of the ϰ agonist bremazocine (ED50 = l0 µg/kg). The similar potency of buprenorphine as an antagonist of bremazocine in naive and morphine-tolerant rats further supports the hypothesis that buprenorphine exerts it's antidiuresis via an antagonistic effect at ϰ sites, rather than as an agonist at the µ sites. The high affinity displayed by buprenorphine at the ϰ opioid receptor in vivo is consistent with this conclusion. Hence, buprenorphine can now be classified as a partial agonist at the µ site and as an antagonist at the ϰ site against bremazocine induced urine flow, while its action at the δ site to which it has much lower affinity in vivo remains unknown.
authors.affiliation: Departments of Pharmacy and Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, California, 94143.
authors.forename: M L
authors.initials: ML
authors.lastname: Richards
authors.forename: W
authors.initials: W
authors.lastname: Sadée