Peripheral cardiovascular alpha- and beta-adrenergic effects of some hypotensive and bradycardic arylalkyl imidazole derivatives in the rat.

In pithed rats, a series of four alkyl bridge analogues of 4(5)-substituted arylalkyl imidazole induced alpha-adrenoceptor-mediated vasoconstriction and inhibition of electrically stimulated tachycardia. These effects were induced in the order of potency clonidine = MPV 207 greater than MPV 295 greater than MPV 304 greater than MPV 390, correlating with the length of the alkyl bridge between the phenyl and imidazole moieties. The peripheral postsynaptic actions of MPV 207 and MPV 304 were attenuated by prazosin (0.1 mg kg-1 i.v.) and yohimbine (1 mg kg-1 i.v.). The pressor responses induced by MPV 295 were antagonized only by yohimbine (0.3 and 1 mg kg-1 i.v.). The peripheral sympathoinhibitory action of these compounds was antagonized by yohimbine (1 mg kg-1 i.v.). In spontaneously beating rat atria, the MPV compounds showed neither agonistic nor antagonistic activity at cardiac postsynaptic alpha- and beta-adrenoceptors. The results indicate that the hypotensive and bradycardic MPV compounds are agonists at peripheral cardiovascular alpha-adrenoceptors. The extension of the alkyl bridge between the phenyl and imidazole moieties reduces their activity at alpha-adrenoceptors. Finally, MPV 295 seems to be a selective agonist of peripheral alpha 2-adrenoceptors in the cardiovascular system of the pithed rat.