Comparison of the calcium antagonistic activity of nifedipine and FR34235 in the canine saphenous vein.
The effects of FR34235 (FR) on contractions and 45Ca2+ uptake stimulated by depolarization (80 mM KCl) and activation of postsynaptic alpha 1-adrenoceptors in the canine saphenous vein (CSV) were studied and compared with those of nifedipine. The 45Ca2+ uptake and contractions evoked by KCl were inhibited in a dose-dependent fashion by FR [concentration producing 50% inhibition [(IC50 = 2.0 +/- 0.5 and 1.2 +/- 0.3 X 10(-8) M, respectively)] and nifedipine (IC50 = 6.0 +/- 1.0 and 4.0 +/- 0.9 X 10(-8) M, respectively). FR was a potent inhibitor of the 45Ca2+ uptake and contractions of CSV induced by the selective alpha 1-agonist, SK&F l-89748 (l-[1,2,3,4-tetrahydro-8-methoxy-5-(methylthio)-2-naphthalenamine] ) (IC50 = 7.2 +/- 0.7 and 7.0 +/- 1.8 X 10(-8) M, respectively). In contrast, the contractions and 45Ca2+ uptake elicited by SK&F l-89748 were much less sensitive to nifedipine (IC50 = 6.0 +/- 1.4 and 6.6 +/- 0.4 X 10(-6) M, respectively). The results suggest the following: (a) both FR and nifedipine are potent antagonists of the voltage-dependent Ca2+ channels in CSV; and (b) FR is a more effective antagonist of receptor-operated Ca2+ entry in the saphenous vein than nifedipine.
K F
KF
Jim
W D
WD
Matthews
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D012501:Saphenous Vein / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D002121:Calcium Channel Blockers; D011942:Receptors, Adrenergic, alpha; D013764:Tetrahydronaphthalenes; C035100:nilvadipine; D011189:Potassium Chloride; C039140:SK&F 89748; D009543:Nifedipine; D002118:Calcium