Urapidil, a multiple-action alpha-blocking drug.
Investigations in animals indicate that urapidil has a number of actions that may be relevant to its antihypertensive effect. It has an alpha 1-blocking action, a weak beta 1-blocking effect, an interaction with a serotonin receptor and a central depression of sympathetic tone. Urapidil is well absorbed orally with a bioavailability of about 70% and a time to peak concentration of about 4 hours after a sustained release capsule. It is metabolized in the liver at a half-life of 4.7 hours. Peripheral alpha 1-blocking activity has been demonstrated in humans. A shift to the right in the dose-response curve to phenylephrine has been found after urapidil, whereas responses to angiotensin are not affected. Evidence for beta 1-blocking activity is marginal. Urapidil does not inhibit the exercise increase in heart rate. Some investigators have suggested a possible inhibition of isoprenaline tachycardia; others have found no evidence. There is some evidence suggestive of a central action of urapidil in humans as lower single doses result in a decrease in blood pressure and an increase in heart rate. With higher doses the hypotensive effect continues but the tachycardia no longer occurs. However, urapidil has been reported to increase noradrenaline levels, although there has been a report with a high dose reducing vanillylmandelic acid excretion. Evidence for changes in renin is inconsistent. Hemodynamic studies have revealed findings that are compatible with peripheral alpha 1 blockade. After intravenous administration, peripheral resistance is reduced along with arterial pressure, and cardiac output is increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Prichard
B N
BN
Department of Clinical Pharmacology, University College and Middlesex School of Medicine, London, United Kingdom.
Tomlinson
B
B
Renondin
J C
JC
D000317:Adrenergic alpha-Antagonists / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism; D010879:Piperazines / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D014655:Vascular Resistance / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D010879:Piperazines; C015568:urapidil