Adrenergic and serotonergic receptor-blocking potencies of terazosin, a new antihypertensive agent, as assessed by radioligand binding assay

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  • Adrenergic and serotonergic receptor-blocking potencies of terazosin, a new antihypertensive agent, as asseased by radioligand binding assay.

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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.

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