Alpha-adrenergic blocking activity of prazosin: Effect on catecholamine levels and catecholamine synthetic enzymes

Abstract Prazosin, a new antihypertensive agent, was demonstrated to be an effective and long lasting α-blocker. In comparison with phenoxybenzamine, prazosin caused a similar hypotensive response but failed to induce tachycardia. Both drugs depleted the norepinephrine content and stimulated an increase in tyrosine hydroxylase activity of the adrenal gland. Also, the norepinephrine content of the heart was decreased by chronic administration of each drug. Cardiac dopamine-beta-hydroxylase activity, although decreased by phenoxybenzamine, was unchanged by prazosin. The effect of prazosin on heart rate and cardiac dopamine-beta-hydroxylase differs from the traditional α-blockers and could reflect the affinity of the drug for the postsynaptic alpha-receptor.