The affinity of morphine for its pharmacologic receptor in vivo

Morphine receptor affinity, an important constant in the classification of opiate receptors, has not yet been determined by a pharmacologic method. In the present study, we used a standard pharmacologic procedure, that of partial receptor occlusion, to make this determination in the rat utilizing the hot water (55 degrees C) tail flick test. The occluding compound was buprenorphine, a new narcotic antagonist analgesic that can bind to opiate receptors in an irreversible manner. When buprenorphine was given to rats in doses of 0.30 and 0.60 mg/kg (s.c.), 30 min before morphine (20-320 mg/kg s.c.) and 60 min before testing, it produced the theoretically predicted alterations in the morphine dose-response relation that are indicative of partial receptor blockade. The morphine receptor apparent dissociation constant (reciprocal of affinity) was calculated to be 1.7 X 10-6 M. This value is greater than those previously obtained in radiolabeled binding studies which have ranged from 3 to 27 X 10-9 M in the absence of sodium chloride to 1 to 5 X 10-7 M in the presence of sodium chloride. Used in this way, buprenorphine may be a valuable tool in the determination of apparent dissociation constants for other narcotic agonists.