Dopropidil is an antianginal calcium ion modulating agent, possessing intracellular calcium antagonist activity and anti-ischemic effects in several predictive animal models. Dopropidil had similar vasorelaxant potency as bepridil in the rabbit aorta depolarized by K(+), but was less potent than verapamil, nifedipine, and diltiazem in this respect. Dopropidil has an unusual pharmacological profile, which includes both antiarrhythmic and anti-atherosclerotic properties. In vitro studies show that dopropidil inhibits both smooth and cardiac muscle contractions induced by activation of voltage operated channels, and inhibits the “slow” inward calcium current in the latter tissue, suggesting that dopropidil blocks membrane calcium ion channels. Dopropidil-induced inhibition of collagen and thrombin-induced platelet aggregation at higher concentrations also suggests actions other than calcium channel blockade since platelets lack voltage operated channels. Dopropidil also reduces fatty streak formation in the aorta of cholesterol fed rabbits, an action which may be related to the demonstrated antioxidant properties of this compound. Long-term toxicity studies in rats and dogs showed only mild toxic signs, notably a decrease in food consumption, slight sedation, and some vomiting in the latter species. Dopropidil had been in phase II clinical trials for the treatment of angina pectoris and arrhythmias. However, these studies were discontinued.