Positive inotropic effect of the novel forskolin derivative 6-(3-dimethylaminopropionyl)forskolin hydrochloride.

The effect of NKH477 (6-(3-dimethylaminopropionyl)forskolin hydrochloride, CAS 138605-00-2), a novel water-soluble forskolin derivative, on the energy metabolism of the heart was examined and compared with that of dobutamine. The isolated rat heart was perfused with Krebs-Henseleit bicarbonate buffer with a gas mixture containing 95% O2 + 5% CO2 according to the Langendorff's technique. NKH477 (1 or 10 mumol/l) increased maximum rate of rise of left ventricular pressure (LVdP/dtmax) (positive inotropic action), heart rate (positive chronotropic action), and coronary flow. On the other hand, dobutamine (50 or 500 nmol/l) exhibited the positive inotropic action only. Both NKH477 (10 mumol/l) and dobutamine (500 nmol/l) increased the tissue adenosine monophosphate level, and decreased the tissue creatine phosphate level (a decrease in energy store) in the heart. Nevertheless, neither NKH477 (1 or 10 mumol/l) nor dobutamine (50 or 500 nmol/l) modified the tissue adenosine triphosphate level and the value of energy charge potential, an index of myocardial energy state. These results suggest that NKH477 produces both positive inotropic and positive chronotropic actions, while it does not disturb myocardial energy state, although it decreases the energy store.