The effects of m-AMSA on rat isolated heart.
m-AMSA (4'[9-acridinylamino]methansulphon-m-anisidide) is a new cytoxic agent now under clinical trial. We used the rat isolated perfused heart model in order to investigate the cardiac effects of m-AMSA. The results of the dose-response study indicate that m-AMSA has an acute moderate negative inotropic effect. The 90% effect (25% decrease in developed force compared to the control) was observed at drug concentration of 1.5 micrograms/ml. The refractory period (as measured by stimuli of twice diastolic threshold intensity) increased progressively as the drug concentration was increased (up to 2.5 micrograms/ml). Measurements of the strength-duration and strength-interval relationship showed that m-AMSA induced a significant reduction (P less than 0.005) in excitability and prolongation of refactoriness. We suggest that m-AMSA has a membranal cardiotoxic effect in addition to its known intracellular cytotoxic effect.
D000609:Aminoacridines / Q000494:pharmacology*; D000677:Amsacrine; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000609:Aminoacridines; D000970:Antineoplastic Agents; D000677:Amsacrine