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

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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 α_1,α_2-, and β-adrenoceptors in the rat orain were examined using radioligand binding assay methods. pA_2 values were also obtained in the isolated rat aorta (α_1-adrenoceptor) using phenylephrine as an agonist. A strong inhibition by these drugs of [^3H] prazosin binding to α_1-adrenoceptors was observed, while the inhibition of [^3H] DHA binding to β-adrenoceptors and [^3H] p-aminoclonidine binding to α_2-adrenoceptor was found to be very weak. The rank order of antagonistic potencies of these drugs against the α_1-adrenergic receptors was determined by inhibition constants (K_i) with SGB-1534=prazosin=bunazosin > terazosin > ketanserin. The pA_2 value of these drugs, in contrast, had prazosin with higher pA_2 value than that of SGB-1534. From these two different types of experiments, it was clear that these drugs antagonized α_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 α_1-adrenoceptors in the central nervous system as in the peripheral tissues.
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