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PubMed · 2569263

Urapidil, a multiple-action alpha-blocking drug.

B N Prichard·B Tomlinson·J C Renondin
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Abstract

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)

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Adrenergic alpha-AntagonistsAgedAged, 80 and overAnimalsAntihypertensive AgentsBiological AvailabilityBlood PressureDose-Response Relationship, DrugHumansKidney DiseasesLiverLiver DiseasesPiperazinesVascular ResistanceJournal ArticleReview

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B N Prichard, B Tomlinson, J C Renondin. 1989-08-15. Urapidil, a multiple-action alpha-blocking drug.. https://doi.org/10.1016/0002-9149(89)90689-9

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PubMed2007

Differential effects of urapidil and doxazosin on heart rate.

OBJECTIVE: Although alpha-blockers are effective in lowering blood pressure, they may increase heart rate, an unwanted effect that could negatively affect outcome. However, the alpha-blocker urapidil might not increase heart rate due to its additional effect on 5-HT1A receptors. Therefore, we compared the effects of urapidil on heart rate with those of another alpha-blocker, doxazosin. METHODS: We performed a randomised, double-blind, placebo-controlled, cross-over study in 12 healthy males who received single oral doses of 60 mg urapidil, 4 mg doxazosin and placebo. Four hours following drug intake, heart rate and blood pressure were measured at rest and during exercise. RESULTS: Both doxazosin and urapidil decreased blood pressure to the same extent. Compared to placebo, resting heart rate was significantly increased by doxazosin (+25%, P < 0.05) but not by urapidil (+12%, n.s.). Resting heart rate with doxazosin was significantly higher than with urapidil (P < 0.05). Similarly, the rate pressure product (RPP) at rest was increased by doxazosin (+17%, P < 0.05) but not by urapidil (+6%, n.s.). CONCLUSIONS: We conclude that the increase in heart rate caused by urapidil is less pronounced than that with doxazosin, a property that might favour urapidil in the treatment of arterial hypertension. In addition, only doxazosin (but not urapidil) increased the RPP at rest, a finding that might be helpful to explain why this drug was never shown to improve outcome in the treatment of arterial hypertension.

Adrenergic alpha-Antagonists↗
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Adrenergic alpha-Antagonists↗
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Adrenergic alpha-Antagonists↗