In vivo receptor binding of opioid drugs at the mu site.
The in vivo receptor binding of a series of opioid drugs was investigated in intact rats after s.c. administration of [3H]etorphine tracer, which selectively binds to mu sites in vivo. Receptor binding was determined by a membrane filtration assay immediately after sacrifice of the animals and brain homogenization. Coadministration of unlabeled opioid drugs together with tracer led to a dose-dependent decrease of in vivo tracer binding. Estimates of the doses required to occupy 50% of the mu sites in vivo established the following potency rank order: diprenorphine, naloxone, buprenorphine, etorphine, levallorphan, cyclazocine, sufentanil, nalorphine, ethylketocyclazocine, ketocyclazocine, pentazocine, morphine. In vivo-in vitro differences among the relative receptor binding potencies were only partially accounted for by differences in their access to the brain and the regulatory effects of Na+ and GTP, which are expected to reduce agonist affinities in vivo. The relationship among mu receptor occupancy in vivo and pharmacological effects of the opioid drugs is described.
Rosenbaum
J S
JS
Holford
N H
NH
Sadée
W
W
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000378:metabolism; D016314:Ethylketocyclazocine; D005048:Etorphine / Q000378:metabolism; D005260:Female; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism*; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D012964:Sodium / Q000494:pharmacology; D014316:Tritium
D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D014316:Tritium; D005048:Etorphine; D016314:Ethylketocyclazocine; D006160:Guanosine Triphosphate; D012964:Sodium; D003496:Cyclazocine