Alpha-blocking potencies of antihypertensive agents (prazosin, terazosin, bunazosin, SGB-1534 and ketanserin) having with quinazoline or quinazolinedione as assessed by radioligand binding assay methods in rat brain.

The comparative effects of antihypertensive agents, quinazoline or quinazolinedione residues (prazosin, bunazosin, terazosin, SGB-1534, and ketanserin), on the binding of [3H]prazosin, [3H]p-aminoclonidine and [3H]dihydroalprenolol([3H]DHA) to alpha 1-, alpha 2-, and beta-adrenoceptors in the rat brain were examined using radioligand binding assay methods. pA2 values were also obtained in the isolated rat aorta (alpha 1-adrenoceptor) using phenylephrine as an agonist. A strong inhibition by these drugs of [3H]prazosin binding to alpha 1-adrenoceptors was observed, while the inhibition of [3H]DHA binding to beta-adrenoceptors and [3H]p-aminoclonidine binding to alpha 2-adrenoceptor was found to be very weak. The rank order of antagonistic potencies of these drugs against the alpha 1-adrenergic receptors was determined by inhibition constants (Ki) with SGB-1534 = prazosin = bunazosin greater than terazosin greater than ketanserin. The pA2 value of these drugs, in contrast, had prazosin with higher pA2 value than that of SGB-1534. From these two different types of experiments, it was clear that these drugs antagonized alpha 1-adrenoceptors even in the central nervous system, and the side chains bound to quinazoline and quinazolinedione residues may play an important role in the antagonistic potencies for alpha 1-adrenoceptors in the central nervous system as in the peripheral tissues.