Effect of 3-[2-[4-(o-Methoxyphenyl)-1-piperazinyl]ethyl]-2, 4(1H, 3H)-quinazolinedione Monohydrochloride (SGB-1534), an Anthihypertensive Agent, on ³H-Prazosin and ³H-p-Aminoclonidine Binding to α₁-and α₂-Adrenoceptors in Dog Brain and Arta

Abstract

In order to assess the antihypertensive activities of SGB-1534, 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl]-2, 4-(1H, 3H)-quinazolinedione monohydrochloride, the effect of this drug on the ³H-prazosin, ³H-p-aminoclonidine and ³H-dihydroalprenolol (³H-DHA) bindings to α₁-, α₂-and β-adrenoceptors in dog brain and aorta was determined by means of radioligand binding assay and compared with that of prazosin. Potent inhibition of ³H-prazosin binding to α₁-adrenoceptor sites in the brain and the aorta by SGB-1534 was observed (the potency in the brain was almost the same as that prazosin), but the inhibition of ³H-p-aminoclonidine and ³H-DHA bindings to α₂-and β-adrenergic binding sites by both SGB-1534 and prazosin was very weak. In addition, a high pA₂ value of α₁-blocking action by SGB-1534 was fornd in a pharmacological experiment. Thus, these results suggest that the inhibitory effect of SGB-1534 at α₁-adrenoceptor binding sites, but not at α₂-or β-adrenozeptor sites, may contribute to the hyprotensive effect.