Differentiation of mu- and kappa-receptors by means of correlation of analgesic potency in vivo and receptor binding affinity in vitro of various opioid agonists.
For various opioid agonists (n = 35) an unsatisfactory correlation between analgesic activity in vivo (mouse) and receptor binding affinity (rat brain) in vitro was obtained. Excellent correlations were observed, however, after separation of the opioid agonists into two groups with mu- and kappa-receptor selectivity, respectively. The correlation of the analgesic potency with the affinity to the opioid kappa-receptor was very high for the group of kappa-agonists, while it was low for the group of mu-agonists. The slopes of the regression lines were near unity and parallel. The shift from the less potent mu-agonists to the more potent kappa-agonists was about one order of magnitude indicating that analgesia of kappa-agonists is mediated by both mu- and kappa-receptors.
D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D000700:Analgesics; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu