Adrenergic and Serotonergic Receptor-Blocking Potencies of Terazosin, a New Antihypertensive Agent, as Assessed by Radioligand Binding Assay

Abstract

To assess the antihypertensive effect of terazosin, 2 [4- (tetrahydro-2-furanyl) carbonyl-l-piperazinyl] -6, 7-dimethoxy-4-quinazolinamine hydrochloride dihydrate, the inhibitory potency of terazosin on ³H-prazosin, ³H-p-aminoclonidine, ³H-dihydroalprenolol (³H-DHA), ³H-serotonin and 3H-ketanserin bindings to α1-, α2-and β-adrenergic receptors and 5HT₁ and 5HT₂ (serotonergic) receptors was examined by using the radioligand binding method. The results were compared with those for prazosin and bunazosin. Dog brain and aorta were used in the present study. A high inhibition of ³H-prazosin binding to α₁-adrenoceptors in dog aorta by terazosin was observed, but the inhibitions of ³H-DHA, ³H-p-aminoclonidine, ³H-serotonin and ³H-ketanserin bindings by this drug were very weak. l-Terazosin showed the greatest inhibitory effect on ³H-prazosin binding to α₁-adrenoceptors in dog aorta and brain. These results suggest that an inhibitory effect of terazosin at α₁-aradrenoceptor binding sites may contribute to the hypotensive effect; the α₂-and β-adrenoceptors and the serotonergic binding sites do not appear to be involved.