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

Abstract

ABSTRACT-The pharmacological profile of a new alpha-adrenoceptor antagonist, , 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 a 1-adrenoceptor-mediated contractions induced by noradrenaline with pA2 values ranging from 6.73 to 8.15. KT-611 also inhibited the postjunctional a2-adrenoceptor mediated contractions in the dog saphenous vein (pA2 = 6.77) or dog basilar artery. However, the responses mediated through prejunctional a2-adrenoceptors (rat vas deferens), /3-adrenoceptors (rat atria), muscarinic receptors (guinea pig ileum) and 5 HT2 receptors (dog mesenteric artery) were little affected by KT-611. KT-611 also in hibited the sympathetic adrenergic contraction evoked by electrical transmural stimu lation 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 pK; values of 7.69 and 5.75, respectively. These results suggest that KT-611 is an a 1-adrenoceptor antago nist with a weak antagonistic activity to postjunctional a2-adrenoceptors.

Naftopidil, A Novel Antihypertensive Drug

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