152802-84-1

EC50: 0.55 μM (K _ATP channel)

KRN4884 (0.3 μM) shifts the concentration-response relationship for ATP-induced K _ATP channel inhibition to the right and slightly upward direction without altering the slope. After either the spontaneous or Ca ²⁺ -induced channel rundown, KRN4884 (1 and 3 μM) partially restores the K _ATP channel activity. Furthermore, the effect of KRN4884 is augmented by the presence of uridine 5′-diphosphate (3 mM). KRN4884 activates cardiac K _ATP channels through not only decreasing the sensitivity of the channel to ATP but also directly stimulating the opening of the channel. KRN4884 (0.3 and 3 μM) increases the outward current in a concentration-dependent manner, and the unitary current amplitudes are similar to that of K _ATP channels in the ATP-free solution.

The effects of KRN4884, a novel pyridinecarboxamidine type K _ATP channel opener, on serum triglyceride levels are investigated in Sprague-Dawley rats. Oral administration of KRN4884 (3 mg/kg) for 10 days causes a significant reduction in serum triglyceride levels, which is comparable to that of Clofibrate (160 mg/kg). Reduction in serum triglyceride levels by KRN4884 and Clofibrate are accompanied by a reduction in triglyceride levels both in chylomicron and in very low density lipoprotein. KRN4884 treatment does not affect serum concentrations of total cholesterol and phospholipid, but increases free fatty acid levels. Rats receiving KRN4884 exhibite an increase in lipoprotein lipase (LPL) activity both in adipose tissue and in skeletal muscle.