Cardiovascular effects of a new inotropic drug in dog and normal man.
Cardiovascular effects of 1-butyl-3(1-(6,7-dimethoxyquinazolin-4-yl) piperidin 4 yl urea) (BDPU) were studied in 16 anesthetized dogs and in 7 healthy male volunteers. In animal experiments intravenous doses of 100, 250, and 500 mug/kg/min produced dose-related, significant increases in cardiac output and peak left ventricular dp/dt. No changes in heart rate and blood pressure occurred at 100 mug/kg/min, whereas higher doses caused falls in both systolic and diastolic blood pressures, accompanied by significant rises in heart rate. Inotropic effects could also be demonstrated in man. Changes of the systolic time intervals were dose-related and began at 64 mug/kg/min. At 250 mug/kg/min, the highest dose administered, the pre-ejection period decreased by 14.8 +/- 4.42 msec and its ratio with left ventricular ejection time by 0.049 +/- 0.017 against their respective control values (p less than 0.01). In contrast to animal experiments, no hypotension or tachycardia was observed in any subject. Pharmacokinetic studies showed a plasma elimination half-life of 76 +/- 3 min (mean +/- SE). There were no subjective side effects and standard laboratory tests were not altered, but there was a slight but significant rise in the urinary enzymes, lactic dehydrogenase (LDH) and glutamic oxaloacetic transaminase (GOT), which persisted up to 7 days.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010880:Piperidines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D011799:Quinazolines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*
D010880:Piperidines; D011799:Quinazolines; C012675:buquineran