Manidipine, (S)- is enantiomer of Manidipine a lipophilic, third-generation dihydropyridine calcium channel antagonist with a high degree of selectivity for the vasculature, thereby inducing marked peripheral vasodilation with negligible cardiodepression. Manidipine has different pharmacological effects and (S)-manidipine is shown to be about 30–80 times more potent than (R)-manidipine in its antihypertensive action and in the radioligand binding assay. Patch-clamp experiments revealed that the S-enantiomers of manidipine displayed a faster onset of action and produced a greater blockade than the R-enantiomer. Also, manidipine enantiomers have markedly different pharmacokinetics and the S/R ratio for (S)- and (R)-enantiomer concentrations is 2.0

Cilnidipine (FRC-8653) is a dihydropyridine (DHP) type of calcium channel antagonist. The L-type Ca2+ channel blockade by cilnidipine affects predominantly vascular smooth muscle, thereby producing vasodilation of peripheral resistance vessels and coronary arteries. The blockade of N-type Ca2+ channels affects predominantly peripheral nerve endings of sympathetic neurons, thereby dilating blood vessels by lowering plasma catecholamine levels. Furthermore, renoprotective and neuroprotective effects as well as cardioprotective action of cilnidipine have been demonstrated in clinical practice or animal examinations. Cilnidipine was originated by Fuji & Rebio Pharmaceutical Co., Ltd. and developed jointly with Ajinomoto for the treatment of hypertension. Cilnidipine has been launched in Japan.

Efonidipine is a 1,4-dihydropyridine derivative for the treatment of hypertension and angina. Efonidipine exerts its antihypertensive and antianginal effects through blocking L- and T-type calcium channels.

Manidipine is a lipophilic, third-generation dihydropyridine calcium channel antagonist with a high degree of selectivity for the vasculature, thereby inducing marked peripheral vasodilation with negligible cardiodepression. In addition, manidipine does not significantly affect norepinephrine levels, suggesting a lack of sympathetic activation. It has a gradual onset of action and a long duration of action enabling once daily administration. Furthermore, manidipine dilates both the efferent and the afferent renal arterioles and appears to have beneficial renal effects unrelated to its antihypertensive effect. Once-daily oral manidipine is an effective and generally well tolerated antihypertensive agent for younger and elderly adult patients with mild-to-moderate hypertension. In particular, in a large double-blind trial, the incidence of ankle oedema was significantly lower in manidipine than in amlodipine recipients. Manidipine is also effective in hypertensive patients with comorbidities, such as type 2 diabetes mellitus and/or renal impairment, and appears to improve insulin sensitivity without affecting metabolic function. Thus, manidipinerepresents a first-line treatment option for patients with essential mild-to-moderate hypertension.

Fendiline or Sensit (N-(3,3-diphenylpropyl)-(1-phenylethyl)-amine), is a diphenylalkylamine blocker of L-type calcium channels. Fendiline is an anti-anginal agent for the treatment of coronary heart disease. Pharmaco-dynamically, it exerts the typical calcium as well as calmodulin antagonistic actions: inhibition of the transmembrane calcium current, smooth muscle relaxation, negative inotropism, cardioprotection, inhibition of calmodulin-activated myosin light-chain kinase and phosphodiesterase. Pharmacokinetics reveal slow onset of action and a long half-life. The anti-anginal and anti-ischaemic efficacy of fendiline has been proven in several placebo-controlled, double-blind trials. Fendiline is an FDA-approved, albeit now clinically obsolete. Additionally, fendiline is a specific inhibitor of K-Ras plasma membrane localization that also inhibits K-Ras signal output and blocks the proliferation of K-Ras-transformed tumor cells.

Prenylamine, a slow Ca2+ channel blocker, was used to treat patients with angina pectoris, but because of the QT prolongation, this drug was withdrawn from the market. Prenylamine binds to calmodulin section and inhibits myosin light chain kinase.

Lomerizine (INN) (also known as KB-2796) is a diphenylpiperazine class L-type and T-type calcium channel blocker with relatively selective CNS effects. Voltage dependent L-type Ca2+ channels play an important role Ca2+ influx. L-type calcium currents typically require a strong depolarization for activation and are long-lasting. The common pharmacological profile of L-type channels is determined by the α1 subunit, which forms the Ca2+ selective. Lomerizine was developed as a potential agent for the selective improvement of the ocular or cerebrovascular circulation with minimal adverse cardiovascular effects, and it is used as an anti- migraine drug. Lomerizine selectively relaxes smooth muscle cells by inhibiting L-type Ca2+ influx, thereby reducing tone and increasing blood flow in cerebral vessels. Lomerizine also shows neuroprotective effects against secondary degeneration resulting from injury in retinal ganglion cells. While some calcium-channel blockers, such as flunarizine, act on the dopaminergic system, lomerizine is ineffective in vivo at inhibiting the release of dopamine. However, it has been observed to weakly inhibit the binding of [3H]spiperone to D2 dopamine receptors in vitro. While researchers are unsure of the reason for this difference, one hypothesis is that the doses administered cannot reach a high enough concentration in the brain to affect D2 receptors.

Gallopamil is a L-type calcium channel blocker designed for the treatment of coronary heart diseases: angina pectoris, prinzmetal angina and hypertonia.

Efonidipine is a 1,4-dihydropyridine derivative for the treatment of hypertension and angina. Efonidipine exerts its antihypertensive and antianginal effects through blocking L- and T-type calcium channels.

Lercanidipine is antihypertensive drugs which acts by blocking L-type calcium channels, allowing relaxation and opening of blood vessels. Lercanidipine exists as a racemate, with anti-hypertensive activity residing primarily in S-enantiomer. NDA for lercanidipine was submitted to FDA in 2002 by Forest Laboratories, but FDA refused to approve the drug, and lercanidipine is not marketed in USA. Lercanidipine is also investigated in preclinical models of epilepsy and ischemic stroke.