Drug affinities for the agonist and antagonist states of the opioid receptor.
Traditional methods of analyzing the binding of opiates do not accurately establish the affinities of the drugs for the agonist and antagonist states of the opioid receptor. The poor results obtained by the Scatchard procedure may be attributed to the presence of extraneous drug binding sites in the brain-homogenate medium. In this study a nonlinear regression technique has been employed to analyze receptor binding in terms of the two-state Snyder-Pert model while simultaneously considering drug association with the aggregate of non-receptor binding sites. Results are reported for naloxone, pentazocine, and dihydromorphine, which respectively represent a pure antagonist, a mixed agonist-antagonist, and a pure agonist. the affinity constants characterizing equilibrium binding at the agonist and antagonist states of the receptor at 37 degrees C are given for each of the three drugs. In addition, a theoretical index, f tau, is defined which provides a measure of the fraction of receptors existing in the agonist state. It is found that the graft of f tau vs log [D] exhibits features similar to the in vivo dose-response curves for the drugs.
D000818:Animals; D001923:Brain Chemistry; D004090:Dihydromorphine / Q000378:metabolism; D066298:In Vitro Techniques; D008956:Models, Chemical; D009270:Naloxone / Q000378:metabolism; D010423:Pentazocine / Q000378:metabolism; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*
D011957:Receptors, Opioid; D009270:Naloxone; D004090:Dihydromorphine; D010423:Pentazocine