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 agonists 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 agonist. SDZ ENS 163 (thiopilocarpine), pilocarpine and McN-A-343 (0.1 microM-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-methylpiperidine methiodide; 8.41) > pirenzepine (8.10) > himbacine (7.34) > or = p-F-HHSiD (para-fluoro-hexahydrosiladifenidol; 7.15) > methoctramine (6.23). This antagonist apparent affinity profile is consistent with the activation of muscarinic M1 receptors.