Comparison of the receptor binding characteristics of opiate agonists interacting with mu- or kappa-receptors.
1 The receptor binding characteristics of various morphine-like and ketazocine-like opiate agonists were measured by inhibition of [3H]-naloxone binding in homogenates of brain and of ileal myenteric plexus-longitudinal muscle of the guinea-pig. No differences were found for the two tissues. 2 The depressant effect of Na+ on the inhibition of [3H]-naloxone binding by opiate agonists varies widely, giving sodium shifts between 5 and 140. The relationship between Na+ concentration and inhibition of binding is non-linear, the magnitude of the sodium shift varying directly with the slope of the regression of log IC50 on log [NaCl]. 3 The sodium shift of ketazocine-like agonists is lower than that of morphine-like agonists but higher than that of opiates with dual agonist and antagonist action. A working hypothesis is proposed which suggests that the kappa-receptors for the ketazocine-like drugs are less susceptible to the Na+ effect than the mu-receptors for the morphine-like drugs. 4 For most of the morphine-like but not the ketazocine-like agonists, a good correlation has been found for the pharmacological activity in the myenteric plexus-longitudinal muscle preparation and the inhibition of binding of [3H]-naloxone at 12 mM Na+. An exception is fentanyl which has a much greater pharmacological potency than may be expected from its potency in inhibiting [3H]-naloxone binding.
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology; D009022:Morphine Derivatives / Q000378:metabolism / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009270:Naloxone / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology
D009022:Morphine Derivatives; D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine; D012964:Sodium