Trichloroacetamidines, a new class of positive inotropic agents.
A series of trichloroacetamidine derivatives, obtained by addition of amines to trichloroacetonitrile, was evaluated for positive inotropic activity on isolated cat heart papillary muscles. Increased contractility, not antagonized by beta-adrenergic blockade with sotalol or reserpine pretreatment, was observed in this assay with a variety of N-substituted trichloroacetamidine derivatives. More extensive pharmacological studies with the 3-indolylmethyl analogue 2 showed that this amidine in dogs, 5 mg/kg iv, produced a positive inotropic effect more pronounced than that of ouabain, 50 microgram/kg iv. Several of the trichloroacetamidines were found to be inhibitors of guinea pig kidney and calf heart Na-K-dependent ATPase and to have specificity for these enzymes different from that of ouabain. Bacterial mutagenic activity was observed with three members, 2,3, and 12, of the series.
D000081:Acetamides / Q000138:chemical synthesis* / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D002415:Cats; D002417:Cattle; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000201:enzymology; D008297:Male; D008566:Membranes / Q000201:enzymology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology; D010210:Papillary Muscles / Q000187:drug effects; D013329:Structure-Activity Relationship
D000081:Acetamides; D000251:Adenosine Triphosphatases