This study investigates the mechanisms of catecholamine-mediated cardiac toxicity by examining the effects of norepinephrine on adult mammalian cardiocytes. The researchers exposed cardiocyte cultures to various concentrations of norepinephrine and observed a concentration-dependent decrease in cell viability, as evidenced by a significant reduction in viable rod-shaped cells and increased release of creatine kinase. The toxicity was significantly reduced by β-adrenoceptor blockade and mimicked by selective β-adrenoceptor stimulation, while α-adrenoceptor stimulation had a less pronounced effect. Norepinephrine also decreased the incorporation of [³H]phenylalanine and [³H]uridine into cytoplasmic protein and nuclear RNA, respectively, indicating reduced anabolic activity. The toxic effects were attributed to cyclic AMP-mediated calcium overload, as demonstrated by increased intracellular cyclic AMP and calcium levels. Pharmacological interventions that increased intracellular cyclic AMP or blocked calcium influx prevented cell toxicity. These findings suggest that catecholamine-induced cardiac toxicity results from cyclic AMP-mediated calcium overload, leading to decreased synthetic activity and cell viability.This study investigates the mechanisms of catecholamine-mediated cardiac toxicity by examining the effects of norepinephrine on adult mammalian cardiocytes. The researchers exposed cardiocyte cultures to various concentrations of norepinephrine and observed a concentration-dependent decrease in cell viability, as evidenced by a significant reduction in viable rod-shaped cells and increased release of creatine kinase. The toxicity was significantly reduced by β-adrenoceptor blockade and mimicked by selective β-adrenoceptor stimulation, while α-adrenoceptor stimulation had a less pronounced effect. Norepinephrine also decreased the incorporation of [³H]phenylalanine and [³H]uridine into cytoplasmic protein and nuclear RNA, respectively, indicating reduced anabolic activity. The toxic effects were attributed to cyclic AMP-mediated calcium overload, as demonstrated by increased intracellular cyclic AMP and calcium levels. Pharmacological interventions that increased intracellular cyclic AMP or blocked calcium influx prevented cell toxicity. These findings suggest that catecholamine-induced cardiac toxicity results from cyclic AMP-mediated calcium overload, leading to decreased synthetic activity and cell viability.