Comparison of the receptor binding characteristics of opiate agonists interacting with mu- or kappa-receptors

Br J Pharmacol. 1978 Dec;64(4):607-14. doi: 10.1111/j.1476-5381.1978.tb17323.x.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Brain / drug effects
  • Female
  • Guinea Pigs
  • Ileum / drug effects
  • Male
  • Morphine / metabolism
  • Morphine / pharmacology
  • Morphine Derivatives / metabolism
  • Morphine Derivatives / pharmacology
  • Muscle Contraction / drug effects
  • Naloxone / metabolism
  • Receptors, Opioid / metabolism*
  • Sodium / pharmacology

Substances

  • Morphine Derivatives
  • Receptors, Opioid
  • Naloxone
  • Morphine
  • Sodium