Abstract: The antagonism effect of sertindole on α₁-AR subtypes was studied by combining radioligand binding saaays in three cloned α₁-AR subtypes stably expressed in human embryonic kidney 293 cells and contractile response experiment in isolated rat blood vessels,The results showed that the affinity for sertindole in the cloned α_1A-AR(pK18.90±0.17) was 69-fold (pK₁ 7.06±0.09) and 132-fold (pK₁ 6.78±0.07) higher that for the cloned α_1D-AR,respectively.The pA₂ values for sertindole in antagonizing NE-induced vasoconstriction in isolated rat aorta and renal artery were shown to fit well to the pK₁ values on cloned α_1D- and α_1A-AR,respectively.Pretreatment of membrane preparations with sertindole for 30 min significantly reduced the maximal binding capacities (B_max) of ¹²⁵IBE2254 to the three cloned α₁-AR subtypes without alteration of affinities(KD values). In the presence of sertindole,the B_max of ¹²⁵IBE2254 binding to the cloned α₁-ARs were not significantly changed,while the K_D values were significantly incressed .Thus,sertindole is a selective irreversible compitive α₁-AR antagonist with α_1A subtype.