A review of the biological effects of prazosin, including recent pharmacological findings

Summary

Prazosin has been shown to be a safe, effective, potent antihypertensive agent that lowers blood pressure in a variety of experimental models of hypertension in animals. Prazosin reduces blood pressure by reducing total peripheral resistance, not cardiac output, and no tolerance occurs to the antihypertensive effect of prazosin. Studies in dogs indicate that, like diazoxide, prazosin would be expected not to exaggerate orthostatic hypotension, at least not to the extent that subjective symptoms would limit its usefulness once tissue autoregulatory mechanisms had time to adjust to the lowered perfusion pressure. Unlike other peripherally acting agents, prazosin does not cause a tachycardia, neither does it increase plasma renin activity or sympathetic nerve traffic. Prazosin sensitizes baroreceptors, but this is not a unique property and will not satisfactorily explain the lack of tachycardia with this agent.

The action of prazosin is confined to the periphery and no central mechanism of action has been found. An effect of prazosin at or beyond the α-adrenoceptor was obtained in both in vivo and in vitro experiments, but receptor-protection experiments have demonstrated that this antagonism is different from that induced by phenoxybenzamine. Prazosin has a unique specificity for postsynaptic α-adrenoceptors, with no presynaptic effect. This results in a novel, effective antihypertensive agent to which there is much less tendency for tachycardia and tolerance to occur. This site of action of prazosin is compatible with those of other antihypertensive agents, such as clonidine, β-blockers and α-methyldopa. This suggests that combination of prazosin with any of these classes of antihypertensive agents should result in more effective lowering of blood pressure.