Pharmacologic profile of urapidil.
Urapidil, a phenylpiperazine-substituted derivative of uracil, is a selective alpha 1-adrenoceptor antagonist and therefore decreases blood pressure and peripheral resistance. Apart from its alpha 1-adrenoceptor-blocking potency, which is somewhat less selective than that of prazosin, urapidil appeared to display substantial central hypotensive activity. Initially, this central mechanism was assumed to be the same as that of clonidine, i.e., agonistic activity toward central alpha 2 adrenoceptors. This view, however, appeared to be incorrect for the following reasons: (1) In radioligand binding studies urapidil did not show any affinity for alpha 2 adrenoceptors; and (2) the central hypotensive activity of urapidil, injected into feline vertebral arteries remained unaffected by the alpha 2-adrenoceptor-blocking agents yohimbine and rauwolscine, which are known to suppress the central hypotensive effect of clonidine. The central hypotensive effect of urapidil so far remains unknown in detail, although a few (but not all) experimental arguments would plead for the 5-hydroxytryptamine (5-HT 1A)-agonistic potency of urapidil as an explanation of its central activity. The central hypotensive mechanism of urapidil will be discussed in more detail later in this issue. A presynaptic alpha 2-agonistic activity can only be demonstrated in certain models but not in the classic pithed rat preparation. It is unlikely to play a relevant role in urapidil's hypotensive activity, and also because of the poor affinity of the drug for alpha 2 adrenoceptors. Finally, a weak beta 1-adrenoceptor activity of urapidil can be demonstrated, but this mechanism is unlikely to contribute significantly to the drug's hypotensive activity.
van Zwieten
P A
PA
Division of Pharmacotherapy, University of Amsterdam, The Netherlands.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006801:Humans; D010879:Piperazines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D010879:Piperazines; D017981:Receptors, Neurotransmitter; C015568:urapidil