The pharmacology of prazosin, an alpha 1-adrenoceptor antagonist and the basis for its use in the treatment of essential hypertension

Abstract

Prazosin was the result of an attempt to find a directly acting vasodilator drug with little or no effect on cardiac output, renin and salt and water metabolism. Clinical studies confirmed that these desirable features were possessed by prazosin in spite of an apparently peripheral mode of action and thus prazosin contrasted strongly with all other agents of this type. Prazosin differs from the classical alpha-adrenoceptor antagonists in possessing marked selectivity for alpha 1-adrenoceptors as opposed to alpha 2-adrenoceptors. This ensures the preservation of the local feedback control of the release of noradrenergic transmitter by the pre-junctional alpha 2-adrenoceptors. This fact appears to be responsible for the therapeutic success of prazosin and why prazosin is the first alpha-adrenoceptor blocking drug to be effective in the treatment of hypertension. The marked selectivity for alpha 1-adrenoceptors makes prazosin invaluable as a research tool, especially as a radioligand for the identification of alpha 1-adrenoceptors.