title: Postjunctional selectivity of alpha-blockade with prazosin, trimazosin, and UK-33,274 in man.
abstract: The effects of 3 quinazoline alpha-adrenoreceptor antagonists, prazosin, trimazosin, and UK-33,274, on lying blood pressure (BP), BP response to 60 degrees tilt, pressor response to noradrenaline, phenylephrine, and exercise (isometric and dynamic) were measured in a double-blind study in 6 volunteers. There was no difference between the effects of prazosin 2 mg, trimazosin 200 mg, and UK-33,274 4 mg on lying and tilted BP or on BP response to exercise. All three drugs competitively antagonised the systolic and diastolic pressor effect of phenylephrine and the systolic pressor effect of noradrenaline. Prazosin and UK 33,274 completely suppressed the diastolic pressor effect of noradrenaline and produced an increase rather than a decrease in heart rate (HR). Trimazosin produced a parallel shift in noradrenaline dose response curves for diastolic pressure ahd HR. Prazosin and UK-33,274, but not trimazosin, therefore, produced effects unlike those previously described with alpha-blockers, e.g., phentolamine. The difference between antagonism of the systolic and diastolic effects suggests that the resistance component of the noradrenaline pressor effect, mediated principally via alpha 1-stimulation, is more effectively blocked than the cardiac component, which depends on venous return and alpha 2-mediated venoconstriction. Prazosin and UK-33,274 are clearly alpha 1-selective. Trimazosin is less selective.
mesh_terms: D000317:Adrenergic alpha-Antagonists; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D017292:Doxazosin; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011224:Prazosin / Q000031:analogs & derivatives / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D010879:Piperazines; D011799:Quinazolines; D010656:Phenylephrine; C005185:trimazosin; D017292:Doxazosin; D009638:Norepinephrine; D011224:Prazosin