ISSN:
1432-1912
Keywords:
5-HT receptors
;
α-Adrenoceptors
;
Urapidil
;
Urapidil derivatives
;
Antihypertensive drugs
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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 α1-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-methylurapidil) for 5-HT receptors were investigated using 3H-8-hydroxy-2-(di-n-propylamino)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 α1- and α2-adrenoceptor radioligands, respectively. Urapidil and its analogues produced half-maximum inhibition of 3H-8-OH-DPAT binding at concentrations of 4 × 10−9 mol/l to 4 × 10−7 mol/l with the following order of potency: urapidil 〈 5-acetyl- 〈 5-formyl- 〈 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 × 10−8 mol/l to 8 × 10−7 mol/l (order of potency: urapidil 〈 5-formyl- 〈 5-acetyl- ≤ 5-methyl-urapidil). The affinity of these analogues for 5-HT1B, 5-HT2 and α2-adrenergic recognition sites was distinctly lower. Urapidil and its congeners clearly discriminate between 5-HT- and between α-receptor subtypes. It is postulated that the high affinity for 5-HT1A receptors as well as for α1-adrenoceptors is relevant to the hypotensive properties of these compounds.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00165749
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