In vitro comparison of the pre- and postsynaptic alpha adrenergic receptor blocking properties of prazosin and tiodazosin (BL5111).

Abstract

Tiodazosin (BL5111) is a structural analogue of prazosin that is currently being evaluated for clinical efficacy in the treatment of hypertension. Like prazosin, tiodazosin was a potent competitive postsynaptic alpha adrenergic receptor antagonist. Although tiodazosin exhibited an affinity for the postsynaptic alpha receptor that was 17 times lower than prazosin, tiodazosin was still 4 times more potent than phentolamine in this regard. Under in vitro conditions, tiodazosin, like prazosin, also produced a noncompetitive antagonism of alpha adrenergic receptors in the portal vein, did not show marked affinity for presynaptic alpha adrenergic receptors, and lacked any measurable direct vasodilator effects (nonreceptor mediated) independent of alpha adrenergic receptor blockade.