Abstract
The effects of chlorpromazine and imipramine at concentrations ranging from 25 to 120 (μm on ATPase activities, as well as calcium binding and uptake abilities of the rat heart subcellular membranes, were studied in vitro. Chlorpromazine significantly decreased calcium binding. Mg 2+ ATPase and Na +−K + ATPase activities of the sarcolemmal fraction, whereas imipramine decreased calcium binding, Ca 2+ ATPase and Mg 2+ ATPase activities. Chlorpromazine also produced significant inhibition of the calcium binding and uptake abilities of the microsomal and mitochondrial fractions, while imipramine depressed the mitochondrial calcium uptake activity only at concentrations of 80 μm or higher. The mitochondrial respiratory and oxidative phosphorylation activities were depressed at high concentrations of these drugs. Since different membrane systems have been considered to be involved in the regulation of heart function and metabolism, the observed decreases in ATPase and calcium-accumulating activities of the heart subcellular membranes may represent one of the molecular mechanisms for the cardiodepressant actions of chlorpromazine and imipramine.
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