Abstract
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 α1, α2-, and β-adrenoceptors in the rat orain were examined using radioligand binding assay methods. pA2 values were also obtained in the isolated rat aorta (α1-adrenoceptor) using phenylephrine as an agonist. A strong inhibition by these drugs of [3H] prazosin binding to α1-adrenoceptors was observed, while the inhibition of [3H] DHA binding to β-adrenoceptors and [3H] p-aminoclonidine binding to α2-adrenoceptor was found to be very weak. The rank order of antagonistic potencies of these drugs against the α1-adrenergic receptors was determined by inhibition constants (Ki) with SGB-1534=prazosin=bunazosin > terazosin > 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 α1-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 α1-adrenoceptors in the central nervous system as in the peripheral tissues.
