Effects of 6-(3-dimethylaminopropionyl)forskolin hydrochloride on energy metabolism in dog hearts in situ.

The effect of NKH477 (6-(3-dimethylaminopropionyl)forskolin hydrochloride, CAS 138605-00-2) [formula: see text], a newly developed forskolin derivative, on mechanical function, carbohydrate metabolism and energy metabolism was examined in the dog heart, and compared with that of dobutamine. Intravenous injection of NKH477 (10 or 30 micrograms/kg) or dobutamine (1 or 3 micrograms/kg) increased the maximum rate of rise of left ventricular pressure (LVdP/dtmax), producing a positive inotropic effect. The duration of the effect of NKH477 was longer than that of dobutamine. In addition, NKH477 (10 or 30 micrograms/kg) increased heart rate (positive chronotropic effect). Nevertheless, neither NKH477 (10 or 30 micrograms/kg) nor dobutamine (1 or 3 micrograms/kg) modified the tissue levels of adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, creatine phosphate and lactate. Glycolytic flux (as expressed by the ratio of ([glucose-6-phosphate] + [fructose-6-phosphate]) / [fructose-1,6-diphosphate]) and redox state (as expressed by the ratio of [lactate] / [pyruvate]) in the myocardial cells were not influenced by NKH477 (10 or 30 micrograms/kg) or dobutamine (1 or 3 micrograms/kg). These results suggest that NKH477 produces both positive inotropic and positive chronotropic effects, while it does not interfere with the myocardial energy and carbohydrate metabolism.