Deviating central hypotensive activity of urapidil in the cat.

Urapidil, a novel antihypertensive drug, as well as possessing a peripheral alpha 1-adrenoceptor antagonistic effect, also has a significant degree of central hypotensive activity. When injected into the left vertebral artery of chloralose-anaesthetized cats the dose-dependent hypotensive effect of the drug was much stronger than after its systemic administration. Prior treatment, also via the vertebral artery, with various receptor antagonists (yohimbine, prazosin, diphenhydramine, metiamide, sulpiride, pirenzepine, R 56413, naloxone) did not antagonize the central hypotensive effect of urapidil administered subsequently. Accordingly, the central hypotensive action of urapidil is not mediated by central receptors of the following types: alpha 2- or alpha 1-adrenoceptors; H1- and H2-histamine; dopaminergic; muscarinic; 5-hydroxytryptamine; opiate. As such the mechanism of the central hypotensive action remains unexplained. It obviously deviates from that of classical centrally acting antihypertensive drugs like clonidine, guanfacine and alpha-methyldopa, which are agonists of central alpha 2-adrenoceptors.