General pharmacological studies on N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate. 3rd communication: effect on cardiovascular system.
In this general pharmacological study of N-[2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165), its effects on the cardiovascular and respiratory systems were studied. SUN 1165, at doses of up to 1.0 mg/kg i.v., had almost no effect. SUN 1165, at doses of 3.0 and 6.0 mg/kg i.v., caused dose-dependent decreases in blood pressure, common carotid, vertebral, coronary, hepatic and femoral artery and portal vein blood flows, cardiac contractility, heart rate and myocardial oxygen consumption. SUN 1165 increased urine volume and urinary excretion of electrolytes in rats at a dose of 100 mg/kg p.o. SUN 1165 decreased renal plasma flow and urinary excretion of electrolytes in anesthetized dogs at 6.0 mg/kg i.v., but at the antiarrhythmic doses (1.0-3.0 mg/kg i.v. in dogs), it had almost no effects on renal function. SUN 1165 had almost no effect on the autonomic nervous systems in anesthetized dogs. These results suggest that SUN 1165 at the antiarrhythmic doses do not have any effects on the respiratory and cardiovascular systems, renal function and autonomic nervous systems in rats and dogs, but that when administered at high doses, it has inhibitory effects on respiratory and cardiovascular system and renal function. In conclusion, SUN 1165 seems to be a novel antiarrhythmic drug relatively free of cardiovascular, respiratory, renal and autonomic effects.
Aisaka
K
K
Laboratory of Experimental Pharmacology, Suntory Institute for Biomedical Research, Osaka, Japan.
Hidaka
T
T
Hattori
Y
Y
Inomata
N
N
Ishihara
T
T
Satoh
F
F
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine; C042288:pilsicainide