Pharmacological studies of imidazoline derivatives. II. Agonistic and antagonistic actions on alpha-adrenoceptors in various smooth muscle preparations.
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.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D006633:Histamine Antagonists; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D006633:Histamine Antagonists; D007093:Imidazoles; D012702:Serotonin Antagonists; D000109:Acetylcholine