Alpha-receptor function changes after the first dose of prazosin.

The effect of oral prazosin on blood pressure and antagonism of phenylephrine-induce blood pressure increase was investigated in six healthy subjects during a dosing interval after the first dose and 3 days after the first dose of the drug. Prazosin lowered standing blood pressure more after the first dose than after the same dose 3 days later, despite similar plasma levels. Blood pressure decrease correlated with plasma prazosin levels during the elimination phase at the first dose, but not after 3 days of therapy. The phenylephrine log dose-response curves shifted to the right after prazosin, which indicates alpha-receptor antagonism of the drug. On day 4, the phenylephrine curve before prazosin dose shifted to the right of the pretreatment curve on day 1, despite very low prazosin plasma levels. On day 4 after after prazosin dosing the phenylephrine dose-response curves were shifted to the left of that on day 1. Our data indicated tolerance to prazosin effect on blood pressure and to phenylephrine agonism after 3 days dosing. Our data suggest that this might be due to desensitization of alpha-adrenoceptors with differential effects of agonists and antagonists.