Effects of Tiodazosin, Prazosin, Trimazosin and Phentolamine on Blood Pressure, Heart Rate and on Pre- and Postsynaptic α-Adrenergic Receptors in the Rat

Subcutaneous administration of tiodazosin (0.1-3 mg/kg), prazosin (0.01-1 mg/kg), trimazosin (10-30 mg/kg) and phentolamine (0.1-3 mg/kg) to conscious spontaneously hypertensive rats (SHR) produced graded decreases in blood pressure with the order of potency being prazosin > tiodazosin > phentolamine > trimazosin. Heart rate was elevated predominantly only by phentolamine and this was consistent with the activity of this agent for both pre- and postsynaptic alpha-adrenergic receptors. In contrast, tiodazosin, prazosin and trimazosin showed selectivity only for postsynaptic alpha-adrenergic receptors. Acute oral administration of tiodazosin and prazosin indicated tiodazosin to be about 1/2 as potent as prazosin. However, chronic administration of equivalent doses of the two compounds for 25 and 52 days via the drinking water indicated approxiately equivalent, sustained reductions in blood pressure. Furthermore, at the end of the 52-day chronic dosing period tiodazosin caused appreciably less alpha-adrenergic receptor antagonist activity than prazosin as assessed by the norepinephrine dose-pressor response profiles. These results indicate that following chronic dosing with tiodazosin in the rat other mechanisms besides alpha-adrenergic receptor antagonist activity are probably contributing to the antihypertensive effect in the rat.