Selective inhibition of responses to carbachol and McN-A-343 in the rabbit vas deferens.

1. The effect of several selective muscarine receptor antagonists were evaluated on the responses of carbachol (CCh) and McN-A-343 (McN) during sympathetic nerve stimulation in the rabbit vas deferens. 2. The muscarine M1 receptor antagonist pirenzepine exhibited similar apparent pKB values for antagonism of the prejunctional inhibitory response of either CCh (pKB, 8.2) or McN (pKB, 8.5) on sympathetic nerve stimulation. 3. The muscarine M2 receptor antagonists, pancuronium and the bisalkyl ammonium compound 'C7/3-phth' were selective inhibitors of the postjunctional facilitatory response produced by CCh on sympathetic nerve stimulation. They were also 17- and three-fold, respectively, less potent against the inhibitory responses of McN on sympathetic nerve stimulation. The apparent pKB value of pancuronium on the inhibitory response produced by CCh did not differ significantly (P greater than 0.05) from that using McN. A similar finding was made for C7/3-phth. 4. Selective blockade of the inhibitory response to CCh with pirenzepine (0.03 or 0.5 mumol/L) did not significantly (P greater than 0.05) modify the apparent pKB value for pancuronium on the facilitatory response of CCh. 5. Selective blockade of the facilitatory response to CCh with a low concentration of pancuronium (0.5 mumol/L) did not significantly (P greater than 0.05) modify the apparent pKB value for pancuronium (30 mumol/L) on the inhibitory response of CCh. 6. It is suggested that CCh and McN activate the same prejunctional M1 muscarine receptor and that pancuronium is the most selective of the muscarine M2 receptor antagonists presently tested in this preparation for distinguishing between muscarine M1 and M2 receptors.