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COMPARISON OF THE RECEPTOR BINDING CHARACTERISTICS OF OPIATE AGONISTS INTERACTING WITH μ‐ OR K ‐RECEPTORS
Author(s) -
KOSTERLITZMM H.W.,
LESLIE FRANCES M.
Publication year - 1978
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1978.tb17323.x
Subject(s) - (+) naloxone , myenteric plexus , morphine , chemistry , agonist , potency , pharmacology , receptor , opiate , antagonist , endocrinology , ic50 , medicine , biology , biochemistry , in vitro , immunohistochemistry
1 The receptor binding characteristics of various morphine‐like and ketazocine‐like opiate agonists were measured by inhibition of [ 3 H]‐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 [ 3 H]‐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 IC 50 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 /c‐receptors for the ketazocine‐like drugs are less susceptible to the Na + effect than the u‐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 [ 3 H]‐naloxone at 12 m m Na + . An exception is fentanyl which has a much greater pharmacological potency than may be expected from its potency in inhibiting [ 3 H]‐naloxone binding.