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Estimation of affinities and efficacies for κ‐receptor agonists in guinea‐pig ileum
Author(s) -
Leff P.,
Dougall I.G.
Publication year - 1989
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.1476-5381.1989.tb11871.x
Subject(s) - potency , antagonism , receptor , guinea pig , pharmacology , affinities , agonist , chemistry , intrinsic activity , opioid receptor , κ opioid receptor , biology , stereochemistry , endocrinology , biochemistry , in vitro
1 Ethylketocyclazocine (EKC) and U50,488H have been employed widely as κ‐receptor agonists in the study of opioid receptor systems. However, the quantification of their agonism in terms of affinities and relative efficacies has not been investigated. 2 In this study, operational model‐fitting was used to analyse the effects of irreversible receptor alkylation by β‐chlornaltrexamine (β‐CNA) on the /c‐receptor mediated effects of EKC and U50,488H in the isolated, coaxially stimulated ileum of the guinea‐pig. 3 EKC produced monophasic inhibitory concentration‐effect curves which were readily amenable to analysis. In contrast U50,488H produced biphasic curves characterized by a higher potency phase of agonism that was susceptible to antagonism by 16‐methylcyprenorphine (RX8008M) and a lower potency phase that was apparently non‐opioid in nature. 4 Analysis of the κ‐receptor‐mediated effects of both agonists indicated that EKC has fifteen fold higher affinity than U50,488H and that the two agonists possess similar intrinsic efficacies.