PHARMACOLOGICAL CHARACTERIZATION OF THE MUSCARINIC RECEPTORS MEDIATING CONTRACTION OF CANINE SAPHENOUS-VEIN

1. The muscarinic receptor subtype mediating contraction of the canine saphenous vein has been characterized using a range of muscarinic ago nists and subtype-selective antagonists. 2, Oxotremorine M and (+)-cis -dioxolane behaved as full agonists, while in comparison L-660,863 /-) -3-(3-amino-1,2,4-oxadiazole-5-yl)quinuclidine) acted as a partial ago nist. SDZ ENS 163 (thiopilocarpine), pilocarpine and McN-A-343 (0.1 mu M-0.3 mM) did not elicit a response. The profile of agonist potencies suggests a low receptor reserve for contraction. 3. The rank order of antagonist apparent affinities was 4-DAMP (4-diphenylacetoxy-N-methyl piperidine methiodide; 8.41) > pirenzepine (8.10) > himbacine (7.34) g reater than or equal to p-F-HHSiD (para-fluoro-hexahydrosiladifenidol; 7.15) > methoctramine (6.23). This antagonist apparent affinity profi le is consistent with the activation of muscarinic M(1) receptors.