Comparison of the calcium-antagonistic effects of terodiline, nifedipine and verapamil.
Studies were carried out on the Ca-antagonistic effects of terodiline and its enantiomers on the potassium-stimulated mesenteric and coronary arteries, on the spontaneous myogenic activity and norepinephrine- and acetylcholine-induced contractions of the protal vein and on electrically stimulated papillary muscle. The effects were compared with those of the Ca-antagonists, nifedipine and verapamil. Terodiline is relatively weak as a Ca-antagonist, having IC50-values between 5 X 10(-6) and 2 X 10(-5)M for all the tissues studied. Nifedipine is the most potent Ca-antagonist on vascular smooth muscle (IC50 3-6 X 10(-9) M), but is considerably less potent on the papillary muscle (IC50 10(-7)M). Verapamil is most potent on the papillary muscle (IC50 7 X 10(-8)M and the portal vein (IC50 6 X 10(-8)M, but is 10 times less potent on the mesenteric and coronary arteries (IC50 3-5 X 10(-7)M). Nifedipine is 1000 times and verapamil and (-)-terodiline 10 times more potent on the slow component of the K-induced contraction while (+/-)- and (+)-terodiline are almost as active on the fast as on the slow component of K-induced contractions on the mesenteric artery. Furthermore, (+/-)-and (+)-terodiline are 10 times more potent in antagonizing acetylcholine- and norepinephrine-induced contractions, whereas (-)-terodiline is equally potent and nifedipine and verapamil are 10 times more potent in blocking the myogenic activity of the portal vein. On the Ca2+-nifedipine and verapamil. However, nifedipine and verapamil, but not terodiline, in concentrations which blocked the maximal norepinephrine-induced response in non-depleted muscle, antagonized the contractions induced by norepinephrine together with Ca2+ in the Ca2+ depleted portal vein. These results show that terodiline blocks the uptake of Ca2+ and, in addition, blocks the utilization of some intracellular stores of Ca2+.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002082:Butylamines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013237:Stereoisomerism; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
D002082:Butylamines; D002121:Calcium Channel Blockers; C010637:terodiline; D014700:Verapamil; D009543:Nifedipine; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine