piperidines and buquineran

1. UK 14,275 (Pfizer) an inotropic agent with cardiac phosphodiesterase inhibitory activity, was administered to ten healthy male volunteers. 2. The inotropic activity was assessed by non-invasive measurement of systolic time intervals (STI). 3. The compound had significant inotropic activity in the doses administered, as judged by the shortening of pre-ejection period (PEP), without any significant chronotropic activity. 4. The inotropic effect was abolished when measurements were repeated following beta-adrenoceptor blockade with oral propranolol. 5. The inotropic activity was compared to that of intravenous isoprenaline.

Topics: Adult; Drug Interactions; Humans; Isoproterenol; Male; Myocardial Contraction; Phosphodiesterase Inhibitors; Piperidines; Propranolol; Quinazolines; Stimulation, Chemical

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.

Topics: Animals; Blood Pressure; Cardiac Output; Dogs; Half-Life; Heart Rate; Hemodynamics; Humans; Male; Myocardial Contraction; Piperidines; Quinazolines