BUPRENORPHINE ANTAGONISM OF MU-OPIOIDS IN THE RHESUS-MONKEY TAIL-WITHDRAWAL PROCEDURE

The apparent in vivo dissociation constant (K-A) and relative efficacy values for alfentanil, etonitazene, morphine, and nalbuphine were det ermined by comparing the effects of these agonists in the presence of buprenorphine with the effects of these agonists alone in the rhesus m onkey tail-withdrawal procedure. Initial time course studies of bupren orphine alone indicated that 3.2 and 10 mg/kg produced increases in ta il-withdrawal latencies when studied with 48 degrees C water for 48 hr . No increases in tail-withdrawal latency were found with either dose studied with 55 degrees C water. Buprenorphine produced dose-dependent shifts to the right for the antinociceptive effects of alfentanil, et onitazene, morphine and nalbuphine 72 hr after administration and decr eased the maximal effects of morphine in 48 degrees C water and those of alfentanil and etonitazene in 55 degrees C water. Buprenorphine adm inistration decreased the receptors available for agonist interaction to approximately 2%. The average apparent in vivo dissociation constan t (K-A) values for alfentanil, etonitazene, morphine and nalbuphine we re 3.3, 0.073, 60 and 31 mg/kg, respectively. High efficacy estimates were determined for alfentanil (149-203) and etonitazene (174-203), wh ereas lower efficacy estimates were determined for nalbuphine (57) and morphine (17). The apparent in vivo dissociation constant of a pseudo irreversible antagonist (K-B) value for buprenorphine averaged 0.15 mg /kg across agonists, temperatures and buprenorphine doses. These data extend and emphasize the significance of in vivo estimates of affinity and relative efficacy for drug classification.