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The effects of 8 imidazoline derivatives on alpha-adrenoceptor-mediated contraction or relaxation of various kinds of smooth muscle preparations were investigated. In rabbit aortic strips, K-6341, K-6343 and K-4011 produced alpha-agonistic action which was antagonized by prazosin. In the study of alpha-antagonistic action of imidazoline derivatives, i.e. antagonism against norepinephrine- or phenylephyrine-induced contraction of the rabbit aortic strip, the order of potency series, prazosin greater than phentolamine greater than yohimbine greater than K-4011, K-3827, K-4300 greater than tolazoline was found. Reserpine pretreatment did not affect the results. In the study of alpha-antagonistic effect on the relaxing response to norepinephrine of methacholine-contracted rat ileum, the potency series was revealed as follows: prazosin greater than phentolamine greater than yohimbine greater than K-4011, K-3827, K-4300, tolazoline. A similar experiment was performed on histamine-contracted guinea-pig taenia coli, and the results were nearly identical to the case of the rat ileum, except that K-6341 and K-6343 also exhibited alpha-antagonistic action which was not detected in the rat ileum. This suggests that alpha 2-receptor may exist in the postsynaptic alpha-adrenoceptor in the guinea-pig taenia coli. The results of the present study indicate that the potency of imidazoline derivatives to inhibit norepinephrine-induced contraction of some smooth muscle is almost identical to that which inhibited norepinephrine-induced relaxation of other smooth muscles. Furthermore, K-4300 was found to possess anti-acetylcholine and anti-histamine actions in the guinea-pig taenia coli and anti-serotonin action in the rat fundus strips.

journal of pharmacobio-dynamics

Pharmacological studies of imidazoline derivatives. II. Agonistic and antagonistic actions on .ALPHA.-adrenoceptors in various smooth muscle preparations.