Urapidil HCl

Urapidil HCl is an α1-adrenoceptor antagonist and 5-HT1A receptor agonist.

[Effects of urapidil and cimetidine on wedged hepatic venous pressure and systemic hemodynamics in cirrhotic patients with portal hypertension].[Pubmed:12828169]

Zhonghua Wai Ke Za Zhi. 2000 Apr;38(4):287-90.

OBJECTIVE: To compare the effects of urapidil and cimetidine on portal pressure and systemic hemodynamics. METHODS: We observed the effects of urapidil (Urapidil HCl, n = 15), cimetidine (n = 20) and placebo (0.9% sodium chloride, n = 10) on wedged hepatic venous pressure (WHVP), hepatic venous pressure gradient (HVPG), and systemic hemodynamics. RESULTS: Urapidil at a dosage of 25 mg intravenously reduced WHVP from 33.33 +/- 7.85 cm H2O to 23.75 +/- 6.83 cm H2O, the average value was 28.75% +/- 9.81% (P > 0.01); and HVPG from 21.92 +/- 2.34 cm H2O to 14.07 +/- 3.57 cm H2O, the average value was 35.81% +/- 8.71% (P < 0.01). The free hepatic venous pressure (FHVP) however was not changed significantly (P > 0.05). The heart rate was increased from 70 +/- 13 BPM to 79 +/- 21 BPM (P < 0.05), and the systolic blood pressure and the diastolic blood pressure were reduced from 122 +/- 40 mm Hg to 95 +/- 32 mm Hg and 75 +/- 17 mm Hg to 55 +/- 15 mm Hg respectively (P < 0.01). After cimetidine administered at a dosage of 400 mg intravenously, WHVP and HVPG were reduced from 34.25 +/- 7.34 cm H2O to 29.05 +/- 7.03 cm H2O and 23.14 +- 8.15 cm H2O to 17.13 +/- 4.28 cm H2O; and the average value was 15.18% +/- 8.64% and 26.00% +/- 12.19% respectively (P < 0.01). But heart rate, blood pressure and FHVP were not altered after use of cimetidine ( P > 0.05). In the control group (n = 10), WHVP, HVPG, FHVP, heart rate, as well as blood pressure were not changed after placebo treatment. CONCLUSIONS: Both urapidil and cimetidine could reduce WHVP and HVPG significantly in cirrhotic patients with portal hypertension, and the effect of the two agents on WHVP and HVPG was not obviously different (P > 0.05). However, the systemic hemodynamic effects induced by urapidil were more significant compared with cimetidine.

Involvement of brain 5-HT1A receptors in the hypotensive response to urapidil.[Pubmed:2569265]

Am J Cardiol. 1989 Aug 15;64(7):7D-10D.

Stimulation of serotonin-1A (5-hydroxytryptamine) (5-HT1A) receptors in the brain stem has been suggested to contribute to the antihypertensive action of the alpha 1-adrenoceptor antagonist urapidil. This hypothesis was tested by analyzing the influence of the 5-HT1A receptor antagonist spiroxatrine on the hypotensive responses to urapidil and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). Chloralose/urethane-anesthetized cats underwent thoracotomy and were artificially ventilated. Blood pressure was monitored in the femoral artery. Urapidil (0.01 to 10 mumol/kg) or 8-OH-DPAT (3 to 30 nmol/kg) was injected into a femoral vein and the maximal hypotensive response recorded. A dose-response test with both drugs was performed before and after administration of spiroxatrine (3 and 10 nmol/kg); the latter was given through the vertebral artery, thus delivering the antagonist to the brain stem. Blood pressure was dose-dependently reduced by urapidil and 8-OH-DPAT after intravenous injection. Central administration of spiroxatrine through the vertebral artery shifted the dose-response curves of both drugs markedly and in a dose-dependent manner to the right, while the hypotensive response to the peripheral vasodilator nitroglycerin remained unchanged. The results suggest that the hypotensive response after peripheral administration of urapidil is mediated in part by stimulation of brain 5-HT1A receptors and this effect on central cardiovascular regulation is additive to the blood pressure reduction resulting from peripheral alpha-adrenoceptor blockade.

Pharmacologic profile of urapidil.[Pubmed:2569262]

Am J Cardiol. 1989 Aug 15;64(7):1D-6D.

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.

Urapidil and some analogues with hypotensive properties show high affinities for 5-hydroxytryptamine (5-HT) binding sites of the 5-HT1A subtype and for alpha 1-adrenoceptor binding sites.[Pubmed:2832770]

Naunyn Schmiedebergs Arch Pharmacol. 1987 Dec;336(6):597-601.

The mechanism responsible for the antihypertensive effect of urapidil is not yet completely understood. Its vasodilator action has been attributed to an antagonism at vascular alpha 1-adrenoceptors. However, it has been suggested that a central action contributes to the hypotensive effect. Recently, three potent analogues of urapidil have been described which also lower blood pressure by a central mechanism. 5-Hydroxytryptamine (5-HT) receptors of the 5-HT1A subtype have been implicated with the central control of cardiovascular function. In the present study, the affinities of these urapidil derivatives (5-acetyl, 5-formyl- and 5-methyl-urapidil) for 5-HT receptors were investigated using 3H-8-hydroxy-2-(di-n-propyl-amino)tetralin (3H-8-OH-DPAT), 125I-iodocyanopindolol (125I-ICYP) and 3H-ketanserin for labelling 5-HT1A, 5-HT1B and 5-HT2 binding sites, respectively. 3H-Prazosin and 3H-clonidine were used as selective alpha 1- and alpha 2-adrenoceptor radioligands, respectively. Urapidil and its analogues produced half-maximum inhibition of 3H-8-OH-DPAT binding at concentrations of 4 x 10(-9) mol/l to 4 x 10(-7) mol/l with the following order of potency: urapidil less than 5-acetyl- less than or equal to 5-formyl- less than 5-methyl-urapidil. Thus, 5-methyl-urapidil is one of the most potent ligands at 5-HT1A recognition sites known to date. The IC50 values of urapidil and its derivatives for 3H-prazosin binding were in the range of 5 x 10(-8) mol/l to 8 x 10(-7) mol/l (order of potency: urapidil less than 5-formyl- less than 5-acetyl- less than 5-methyl-urapidil).(ABSTRACT TRUNCATED AT 250 WORDS)