Clinical pharmacology of urapidil.

Animal investigations suggest that the mechanism of the antihypertensive effect of urapidil may be complex. Suggestions have included an alpha 1-blocking action, a weak beta 1-blocking effect, an interaction with a serotonin receptor and a central depression of sympathetic tone. Peripheral alpha 1-blocking activity has been demonstrated in man, and a shift to the right in the dose-response curve to phenylephrine has been found after administration of urapidil, while responses to angiotensin are not affected. Evidence for beta 1-blocking activity is marginal, but urapidil does not inhibit the exercise-induced increase in the heart rate, and there is only some suggestion of a possible inhibition of isoprenaline-induced tachycardia. Possible central activity may be deduced from the observation that while lower single doses reduce blood pressure and increase the heart rate, with higher doses the hypotensive effect continues but the tachycardia no longer occurs. However, lower doses of urapidil lead to an increase in noradrenaline levels, while changes in renin are less constant, but there has been a report that a high dose reduced vanillylmandelic acid excretion. Urapidil reduces peripheral resistance along with arterial pressure, and cardiac output is increased. In spite of a reduced arterial pressure, renal blood flow is maintained, presumably due to dilation of renal vessels. Urapidil is well absorbed orally with a bioavailability of about 70% and a tmax at about 4 h after a sustained release capsule. It is metabolized in the liver with a t1/2 of 4.7 h. In conclusion there is evidence that urapidil is an alpha 1-blocking drug in man.(ABSTRACT TRUNCATED AT 250 WORDS)