Antihypertensive and Adrenoceptor Blocking Properties of new Sulfonamide-Substituted Phenylethylamines

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Abstract
Studies on the structure-activity relationship using 9 new 3-sulfamoylphenylethylamines revealed that YM-09538, YM-09649 and YM-09686 were competitive antagonists at both β- and postsynaptic α-receptors. The following order of adrenoceptor blocking activities was obtained: propranolol > labetalol > YM-09538 > YM-09649 > YM-09686 for β-receptors and prazosin > YM-09686 > YM-09649 > YM-09538 > phentolamine > labetalol for postsynaptic α-receptors. In contrast to phentolamine, three YM-compounds showed low affinities for presynaptic α-receptors simil ar to prazosin and labetalol. These antagonists except propranolol effectively lowered blood pressure in conscious SHR and their relative effectiveness parallels the postsynaptic α-blocking activity. At hypotensive doses, phentolamine markedly and prazosin, YM-09686 and YM-09649 moderately increased heart rate, whereas YM-09538 and labetalol failed to increase the rate. These results indicate that the postsynaptic α-blocking activity of YM-compounds contributes to their hypotensive activities and that both β-blocking and low presynaptic α-blocking activities contribute to attenuation of the tachycardia.