In vivo RECEPTOR BINDING OF THE OPIATE PARTIAL AGONIST, BUPRENORPHINE, CORRELATED WITH ITS AGONISTIC AND ANTAGONISTIC ACTIONS

1 In order to gain more insight into the mechanisms behind the actions of opiate partial agonists, an analysis of the dual agonist/antagonist properties of the partial agonist, buprenorphine, was made in conjunction with in vivo binding studies of the drug in the rat. 2 Buprenorphine revealed a bell‐shaped dose‐response curve for antinociception peaking at approx. 0.5 mg/kg subcutaneously. It antagonized morphine antinociception at doses which normally have agonistic effects and produced maximum antagonistic effects at doses above those having prominent agonistic activity. The withdrawal precipitating potency of buprenorphine as measured in highly morphine‐dependent rats was present at doses above those having agonistic activity. The entire dose‐response curve for buprenorphine was shifted symmetrically to the right by the opiate antagonist, naltrexone. 3 The dose‐dependent occupation of receptors in vivo by buprenorphine seemed to be almost complete over the agonist dosage range; almost no further receptor occupation over the antagonist range was seen. 4 The possibility is discussed that site‐to‐site receptor interactions leading to cooperativity of effect may be the best explanation of these results.