Pharmacological profile of the novel .ALPHA.-adrenoceptor antagonist KT-611(naftopidil).

Abstract

The pharmacological profile of a new alpha-adrenoceptor antagonist, KT-611 (naftopidil), was studied in vitro. In the dog mesenteric and carotid arteries and in the rabbit, guinea pig and rat thoracic aortae, KT-611 competitively inhibited alpha 1-adrenoceptor-mediated contractions induced by noradrenaline with pA2 values ranging from 6.73 to 8.15. KT-611 also inhibited the postjunctional alpha 2-adrenoceptor-mediated contractions in the dog saphenous vein (pA2 = 6.77) or dog basilar artery. However, the responses mediated through prejunctional alpha 2-adrenoceptors (rat vas deferens), beta-adrenoceptors (rat atria), muscarinic receptors (guinea pig ileum) and 5-HT2 receptors (dog mesenteric artery) were little affected by KT-611. KT-611 also inhibited the sympathetic adrenergic contraction evoked by electrical transmural stimulation in the dog mesenteric artery, and the inhibition was not relieved upon repetitive washing for 1 hour with the drug-free solution. 3H-prazosin and 3H-clonidine binding to the rat cortex membranes was inhibited by KT-611 with pKi values of 7.69 and 5.75, respectively. These results suggest that KT-611 is an alpha 1-adrenoceptor antagonist with a weak antagonistic activity to postjunctional alpha 2-adrenoceptors.