[Pharmacological profile of F-0401, a novel dihydropyridine derivative. (1) Mechanisms of action].
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 x 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 x 10(-7) M) and [3H]PAF binding to rabbit platelets (Ki value: 1.4 x 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.
Kase
N
N
Pharmaceuticals Research Laboratories, Fujirebio, Inc., Tokyo, Japan.
Takasaki
K
K
Higashide
Y
Y
Tamura
N
N
Lee
B
B
Yamaura
T
T
Ohnishi
H
H
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009568:Nitrendipine / Q000037:antagonists & inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D004095:Dihydropyridines; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; C082341:F 0401; D009568:Nitrendipine; D010741:Phospholipases A; D013930:Thromboxane-A Synthase