Cardiovascular and antihypertensive actions of 1-methyl-3-keto-4-phenylquinuclidinium bromide.
The sympatholytic and norepinephrine depleting drug 1-methyl-3-keto-4-phenylquinuclidinium bromide (MA540) possessed significant chronic antihypertensive activity in mecamylamine- and renal-hypertensive dogs. The compound was approximately four times more potent than guanethidine in the former model and three times as potent in the latter. MA540 reduced orthostatic blood pressure responses in unanesthetized rabbits, but was approximately ten times less potent than guanethidine. The quinuclidine derivative did not affect cardiac output, heart rate or stroke volume in anesthetized open chest dogs and moderately increased mean blood pressure and total peripheral resistance. It produced diuresis and saluresis in anesthetized dogs, but did not influence water or electrolyte urinary excretion in conscious rats. In the latter test, guanethidine produced antidiuresis and antisaluresis. It was concluded that MA540 is a potent, orally effective antihypertensive agent acting through adrenergic neuron blockade, that it lacks undesirable effects on cardiac and renal functions, and that compared with guanethidine, it is more potent in lowering blood pressure but less so in interfering with orthostatic cardiovascular reflexes.
D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D011187:Posture; D011311:Pressoreceptors / Q000187:drug effects; D011812:Quinuclidines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats
D000959:Antihypertensive Agents; D011812:Quinuclidines; D006145:Guanethidine