Siratiazem [LRA 113] is a calcium channel antagonist that is structurally similar to diltiazem but has a branched alkyl group on the basic nitrogen. Siratiazem has been developed in an attempt to limit the in vivo N-demethylation that is known to occur with diltiazem. Preliminary binding and functional studies in cardiac and vascular tissues indicate that it not only binds to diltiazem binding sites but also exhibits Ca2+ channel blocking properties comparable to diltiazem. Siratiazem has a similar profile of activity to its parent compound, diltiazem, in that it blocks calcium channels in vascular, intestinal smooth muscle and cardiac tissue, and is least potent in cardiac muscle. At higher concentrations, siratiazem may also block cardiac sodium channels.

Diproteverine is a calcium channel blocking agent. Diproteverine provoked a dose-dependent inhibition of LHRH-stimulated luteinizing hormone release. Diproteverine does not modify mean blood pressure. Diproteverine administered with and without pharmacologic autonomic blockade in the conscious dog causes dose-related depressant effects on sinus node function and atrioventricular conduction without producing significant vasodilatation. Diproteverine caused a redistribution of the available coronary blood flow, to the benefit of an ischemic area of the myocardium. The combination of the reduction in heart rate, to lower cardiac oxygen demand, with the beneficial action on coronary blood flow should result in diproteverinebeing particularly beneficial for the treatment of angina pectoris.

Piprofurol is a benzofuran chalcon derivative. It is a calcium channel blocker. Piprofurol inhibited in a concentration-dependent manner the calcium-induced contractions in isolated potassium depolarized preparations of rat aorta and relaxed the K+-induced contraction of the dog coronary artery and the rabbit basilar artery. Piprofurol also inhibited noradrenaline-induced vascular smooth muscle contractions but the antagonism was clearly noncompetitive and the contractions induced were altered by concentrations two orders of magnitude higher than the concentration inhibiting calcium-induced contractions. Piprofurol exerts a negative inotropic effect on guinea-pig papillary muscle. These effects suggested a potentially anti-ischemic activity. This is confirmed in anaesthetized dogs, where piprofurol reduced the epicardial ST-segment elevation following coronary artery occlusion, and in isolated heart preparations, where it decreased the leakage of LDH during periods of anoxia and reoxygenation. Piprofurol is a coronary vasodilator and antihypertensive agent.

Nictiazem, diltiazem derivative, is a calcium channel blocker. Calcium antagonists and compounds which lower intraocular pressure may be combined in ophthalmic compositions to treat glaucoma.

Falipamil (AQ-A 39), a bradycardiac agent is a calcium channel antagonist. Falipamil can be used to normalize sinus rate in patients with sinus tachycardia of various origin, particularly in intensive care, in acute ischemic heart disease, in anesthesia, and in surgery cases. Falipamil development has been discontinued.

Belfosdil (or SR-7037) is an antihypertensive calcium channel blocker.

Vintoperol (also known as RGH 2981), a peripheral circulation-enhancing compound that was developed as a moderate serotonin and calcium channel antagonist. Vintoperol was studied for the treatment of arterial occlusive disease and peripheral vascular disorders. It was shown that this compound interfered with platelet aggregation both in vitro and in vivo and possessed potent antithrombotic effects in thrombosis models in which platelet activation was mainly involved. Vintoperol participated in phase II clinical trials in Japan for the treatment patients with arterial occlusive disorders, peripheral vascular disorders, and thrombosis. However, because of its toxic side effects, vintoperol was discontinued from the clinical practice.

Mesudipine, a dihydropyridine analog, is a calcium antagonistic drug (slow channel blocker). It blocks electrical activity in smooth muscle cells and Purkinje fibers.

Dotarizine was developed as antimigraineur. Dotarizine inhibited the 5-HT2A response in a concentration-dependent manner. The mechanism of blockade by dotarizine of cerebral vessels contractility has three components: (i) presynaptic inhibition of noradrenaline release; (ii) blockade of postsynaptic vascular 5-HT receptors; (iii) blockade of Ca(2+)entry into the vascular smooth muscle cell cytosol. The compound does not affect the vascular receptors for noradrenaline, angiotensin II or prostaglandin F(2alpha). Dotarizine had a pronounced protective effect against electric seizures.

Carboxyamidotriazole (L651582) is a carboxyamide-amino-imidazole compound originally developed as a coccidiostat, an antiprotozoal agent that acts upon Coccidia parasites. Carboxyamidotriazole (L651582) is an orally-active agent with potential antineoplastic activity. Carboxyamidotriazole binds to and inhibits non-voltage-operated Ca2 channels, blocking both Ca2 influx into cells and Ca2 release from intracellular stores and resulting in the disruption of calcium channel-mediated signal transduction and inhibition of vascular endothelial growth factor (VEGF) signaling, endothelial proliferation, and angiogenesis. This agent may also inhibit tumor cell growth, invasion, and metastasis.