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alpha 1-Adrenoceptor agonist activity of alpha 2-adrenoceptor antagonists in the pithed rat preparation.

The selective alpha 2-adrenoceptor antagonist, RX781094, evoked a dose-related pressor response in the pithed rat preparation when administered in bolus doses by the intravenous route. This response was enhanced following depletion of endogenous amines by reserpine, and inhibited by the selective alpha 1-adrenoceptor antagonist, prazosin. Two other selective alpha 2-adrenoceptor antagonists, Wy26703 and Wy26392, had no marked effect on the blood pressure of this preparation. Pretreatment of the preparation with Wy26703 had no significant effect on the pressor response evoked by RX781094. It is concluded that RX781094 is an alpha 1-adrenoceptor agonist at similar doses to those at which it exhibits alpha 2-adrenoceptor antagonist properties. The agonist activity exhibited by RX781094 is not a general property of all alpha 2-adrenoceptor antagonists and should be considered when this compound is employed as an alpha 2-adrenoceptor antagonist.