Abstract
F-0401 is a novel dihydropyridine (DHP) derivative with potent vasodilative and anti-aggregatory actions. In the present study, we examined the mechanisms of the actions of F-0401 and obtained the following findings: F-0401 suppressed [3H] nitrendipine binding to rat heart membrane (Ki value: 2.2×10-7 M). CaCl2-induced contractions of rabbit aorta and guinea pig taenia coli were inhibited by F-0401 (pA2 values: 7.7 and 6.6). These results indicated that F-0401 had calcium antagonistic activity slightly less potent than that of the other DHP derivatives. In addition, F-0401 significantly inhibited the activity of thromboxane (TX) A2 synthetase (IC50 value: 2.5×10-7 M) and [3H] PAF binding to rabbit platelets (Ki value : 1.4×10-8 M). The other DHP derivatives tested did not affect TXA2 synthetic activity, and the PAF antagonism of the other derivatives were less than that of F-0401. Neither F-0401 nor the other DHP derivatives inhibited cAMP- or cGMP-dependent phosphodiesterase activity. These results revealed that F-0401 has calcium antagonistic, anti-PAF and TXA2 synthetase inhibitory actions in the same dose ranges.
