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Interaction of some muscarinic agonists and antagonists at the prejunctional muscarinic receptor in the rabbit ear artery preparation
Author(s) -
Choo L.K.,
Mitchelson F.,
Vong Y.M.
Publication year - 1986
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.1476-5381.1986.tb14591.x
Subject(s) - muscarinic acetylcholine receptor , agonist , carbachol , chemistry , endocrinology , muscarinic acetylcholine receptor m3 , medicine , muscarinic acetylcholine receptor m2 , pharmacology , muscarinic agonist , muscarinic acetylcholine receptor m1 , muscarine , yohimbine , schild regression , antagonist , receptor , biology , biochemistry
1 The inhibitory effect of several muscarinic agonists on responses to sympathetic nerve stimulation of the isolated perfused ear artery of the rabbit was compared to that of acetylcholine in preparations pretreated with dyflos, cocaine and yohimbine. 2 In general the potency of the agonists was similar to that observed at peripheral muscarinic sites except for arecaidine propargyl ester and 4‐( m ‐chlorophenylcarbamoyloxy)‐2‐butynyl trimethylammonium chloride (McN‐A‐343). The inhibitory effect observed with N‐benzyl‐3‐pyrrolidyl acetate methobromide (AHR‐602) was not exerted via muscarinic receptors. 3 With carbachol (CCh) as an agonist, the antagonist 4‐diphenylacetoxy‐ N ‐methylpiperidine methiodide (4‐DAMP) was found to have a pK B value of 7.74 and thus was 19 fold less active as an antagonist of responses to the agonist, than previously reported for guinea‐pig ileum. When McN‐A‐343 was used as the agonist, the slope of the Schild plot with the antagonist was significantly less than unity. It is suggested that an allosteric interaction of 4‐DAMP may be involved with this agonist. By use of an allosteric model, a pK B of 8.56 for 4‐DAMP was obtained. 4 Secoverine produced similar pK B values with either CCh (8.19) or McN‐A‐343 (8.13) as the agonist.