Van Zwieten P A, Bruning T A
Department of Pharmacotherapy, Academic Medical Centre, Amsterdam, The Netherlands.
Blood Press Suppl. 1994;4:19-24.
The possible role of peripheral 5HT1A-receptors in the vasodilation caused by urapidil was studied by means of venous occlusion plethysmography in the forearm vascular bed of healthy volunteers. Urapidil is known to be an alpha 1-adrenoceptor antagonist and an agonist of 5HT1A-receptors. The hemodynamic effects of urapidil were compared with those of flesinoxan, a selective 5HT1A-receptor agonist virtually devoid of alpha 1-adrenoceptor antagonistic activity, and with the selective alpha 1-adrenoceptor antagonist doxazosin, which has no affinity for 5HT1A-receptors. Urapidil, as well as doxazosin, caused a dose-dependent decrease in forearm vascular resistance (FVR), thus reflecting vasodilation. Both urapidil and doxazosin were competitive antagonists of the vasoconstrictor effect of the selective alpha 1-adrenoceptor agonist methoxamine. On a molar base doxazosin proved more potent than urapidil (more than 10-fold). Flesinoxan slightly decreased FVR only at high doses. The nitric oxide (NO)-synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA) depressed the vasodilatation caused by serotonin and also that by high-dose flesinoxan. The serotonin-induced vasodilatation is known to be NO-dependent. From the experiments it is concluded that peripheral 5HT1A-receptors cannot play an important role in the vasodilator response caused by urapidil, which is predominantly the result of postsynaptic alpha 1-adrenoceptor blockade. 5HT1A-receptors are clearly not involved in the NO-dependent dilatation caused by serotonin. During chronic treatment of hypertension with urapidil central but not peripheral 5HT1A-receptors may be assumed to play a role.
