The effect of dilazep, a potentiator of the adenosine-mediated effects, on the palmitoyl-L-carnitine (PALCAR)-induced mechanical derangement was studied in the isolated rat heart and compared with that of K-7259, a dilazep derivative having less potentiating action on the adenosine-mediated effects. The heart was perfused aerobically by the Langendorff's technique at a constant flow and driven electrically. PALCAR (5 microM) decreased the left ventricular developed pressure and increased the left ventricular end diastolic pressure in the heart (i.e., mechanical dysfunction). These mechanical alterations induced by PALCAR were attenuated by dilazep (1 microM) and K-7259 (1 microM). In contrast, adenosine (10 or 100 microM) did not attenuate the PALCAR-induced mechanical derangement. On the other hand, neither dilazep nor K-7259 modified the mechanical function of the normal (PALCAR-untreated) heart. These results suggest that dilazep and K-7259 attenuate the PALCAR-induced mechanical derangement and that the protective action of both drugs is not due to potentiation of adenosine-mediated effects.