Profile of a new prazosin congener, BL-5111A. Studies in the rat

1. The effects on blood pressure and heart rate of prazosin and a structurally-related congener, BL-5111A, were compared in conscious and anaesthetized rats. 2. Both agents induced dose-related falls in systolic and diastolic blood pressure, with relatively little effect on heart rate. The hypotensive potency of prazosin was twenty-fold greater than that of BL-5111A. 3. The hypotensive activity of prazosin was abolished by pretreatment with the ganglionic blocking agent, pentolinium, or the alpha-adenoceptor blocking agent, phentolamine, whereas BL-5111A retained significant hypotensive activity (up to 28%) after either pretreatment. 4. Both prazosin and BL-5111A attenuated pressor responses to noradrenaline, and reversed the responses to adrenaline, prazosin being, in this respect, 6 times more potent than BL-5111A. There was a highly significant relationship between the alpha-adrenoceptor blocking activity of either agents and its hypotensive effect. 5. BL-5111A differed from prazosin in possessing, in addition to its predominant alpha-adrenoceptor blocking action, a minor component of action attributable to direct vasodilatation.