Peripheral cardiovascular α- and β-adrenergic effects of some hypotensive and bradycardic arylalkyl imidazole derivatives in the rat

Abstract

In pithed rats, a series of four alkyl bridge analogues of 4(5)‐substituted arylalkyl imidazole induced α‐adrenoceptor‐mediated vasoconstriction and inhibition of electrically stimulated tachycardia. These effects were induced in the order of potency clonidine = MPV 207 > MPV 295 > MPV 304 > 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 α‐ and β‐adrenoceptors. The results indicate that the hypotensive and bradycardic MPV compounds are agonists at peripheral cardiovascular α‐adrenoceptors. The extension of the alkyl bridge between the phenyl and imidazole moieties reduces their activity at α‐adrenoceptors. Finally, MPV 295 seems to be a selective agonist of peripheral α₂‐adrenoceptors in the cardiovascular system of the pithed rat.