Elgodipine (IQB-875, CAS 119413-55-7) is a phenyldihydropyridine derivative acting as a calcium channel antagonist. Elgodipine inhibited both T- and L-type calcium channels in a concentration-dependent manner. Elgodipine was in clinical trials for the treatment of cardiovascular diseases however its development has been discontinued.

Niludipine (Bay-a-7168) is a potent calcium antagonistic coronary vasodilator with less cardiodepressant effect than nifedipine. Niludipine is a safe antianginal Ca2+-antagonist with broad effectiveness for various types of angina pectoris. Niludipine is clinically useful as coronary vasodilator and hypotensive agent.

Tamolarizine (also known as NC-1100), an organic Ca2+ channel blocker, was studied in clinical trials phase II in patients with neurological disorders. However, these studies were discontinued. In addition, experiments on rodents have shown that tamolarizine treatment protected the hippocampus from ischemic brain damage and ameliorated place learning impairment. Tamolarizine was also able to reverse the multidrug-resistance phenotype in human leukemia K562 cells through direct interaction with P-glycoprotein.

Nexopamil [LU 49938] is the (S)-enantiomer of a phenylalkylamine derivative and has calcium channel blocking and serotonin2 receptor antagonist activity. Nexopamil's significant antifibrillatory effect during both coronary artery occlusion and abrupt reperfusion is reliably tracked by T-wave alternans magnitude. Because the major component of the protection could be reproduced by blockade of the L-type calcium channel with diltiazem, nexopamil's antiarrhythmic action appears to be due mainly to blockade of this channel. Nexopamil's antiplatelet action through blockade of 5-HT2 receptors may confer additional protection against reperfusion arrhythmias. Nexopamil was discontinued in phase 2 for angina pectoris in European Union.

Cloxacepride is an amide of the dopamine antagonist metoclopramide. It was discovered in the 1980s by Merkle and Panlabs and was found to possess anti-allergic properties. Cloxacepride demonstrated activity in a rat Passive Cutaneous Anaphylaxis (PCA) model after oral administration. Cloxacepride did not protect against histamine-induced anaphylaxis in guinea pigs, thus it was concluded that the effect of cloxacepride is not mediated by histamine receptors. In experiments with human mast cells from adenoidal tissues, cloxacepride at concentrations 10-100 uM significantly inhibited concanavalin A (con A) induced histamine release. At higher concentrations, cloxacepride caused the release of histamine. These findings indicate that cloxacepride acts through calmodulin antagonism.

Dagapamil is a calcium-channel blocker, discovered by BASF. The compound is claimed to have antihypertensive, antiarrhythmic, cardioprotective, antiallergic and platelet aggregation-inhibiting action in animal models.

Clentiazem is a chloride derivative of diltiazem, originated in Tanabe Seiyaku. It works as a blocker of calcium channels. The drug was investigated in the clinical trials for the treatment of stable angina, and essential hypertension. Despite the positive results of clinical trials, no development of the drug was reported.

Lifarizine is a use- and voltage-dependent antagonist of human voltage sensitive sodium currents. Lifarizine inhibited both the plateau and the spike phases of the Ca2+ increases suggesting that, in addition to its known sodium channel blocking properties, it may also inhibit more than one class of calcium channel in the synaptosomes. Lifarizine reduced both infarct area and volume in the mouse with middle cerebral artery occlusion. Lifarizine was in phase II for the treatment of stroke but this investigation was discontinued.

Monatepil is a calcium antagonist that, as do existing calcium antagonists, inhibits the influx of extracellular Ca 2 + through voltage-dependent Ca 2 + channels. It is a new type of antihypertensive agent. Its unique chemical structure was specially designed with intrinsic calcium antagonist and a1 -adrenoceptor-blocking moieties, creating a dual mechanism of action. Positive effects on plasma lipid metabolism are derived from the a1 -adrenoceptor-blocking activity and the antiatherosclerotic effect derives from the calcium antagonist properties. The novel structure of monatepil produces a slow onset of action and a long-lasting antihypertensive effect in experimental animals.

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.