An α1-AR antagonist and 5-HT1A receptor partial agonist
Urapidil is an antagonist of α1-adrenergic receptors (α1-ARs) and a partial agonist of the serotonin (5-HT) receptor subtype 5-HT1A.1,2 It selectively binds to α1- over α2-ARs (IC50s = 0.74 and 42 μM, respectively) and to 5-HT1A over 5-HT1B and 5-HT2 receptors (IC50s = 0.4, 20.4, and >10 μM, respectively) in rat cortex.1 Urapidil inhibits cAMP accumulation induced by forskolin in calf hippocampus as a functional model for 5-HT1A receptors (EC50 = 390 nM).3 It is also a β1-AR antagonist that inhibits the positive chronotropic response induced by isoproterenol in isolated rat atria (pA2 = 6.05).4 Urapidil (1 μmol/kg, i.v.) lowers mean arterial pressure (MAP) in anesthetized cats, an effect that is reduced by central administration of the 5-HT1A receptor antagonist spiroxatrine.5
1.Gross, G., Hanft, G., and Kolassa, N.Urapidil and some analogues with hypotensive properties show high affinities for 5-hydroxytryptamine (5-HT) binding sites of the 5-HT1A subtype and for α1-adrenoceptor binding sitesNaunyn Schmiedebergs Arch Pharmacol.336(6)597-601(1987) 2.van Zwieten, P.A.Pharmacologic profile of urapidilAm. J. Cardiol.64(7)1D-6D(1989) 3.Schoeffter, P., and Hoyer, D.Centrally acting hypotensive agents with affinity for 5-HT1A binding sites inhibit forskolin-stimulated adenylate cyclase activity in calf hippocampusBr. J. Pharmacol.95(3)975-985(1988) 4.Verberne, A.J., and Rand, M.J.Effect of urapidil on β-adrenoceptors of rat atriaEur. J. Pharmacol.108(2)193-196(1985) 5.Kolassa, N., Beller, K.D., and Sanders, K.H.Involvement of brain 5-HT1A receptors in the hypotensive response to urapidilAm. J. Cardiol.64(7)7D-10D(1989)
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