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channel blocker, was used to treat patients with angina pectoris, but because of the QT prolongation, this drug was withdrawn from the market.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.

Dimebon (latrepirdine) is an orally available, small molecule, gamma carboline derivative that was developed and used in Russia as an over-the-counter oral antihistamine for allergy treatment since 1980s. In 1990s it was shown that Dimebon has promising potential in treating neurodegenerative diseases. In 2003, Medivation Inc acquired the rights to Dimebon. Medivation went public in December 2004, with Dimebon as the only drug in its pipeline. The product was being developed by Medivation and Pfizer as a treatment for early-stage Alzheimer's disease and Huntington's disease. However, development was discontinued by Medivation and Pfizer in early 2012. Dimebon inhibits alpha-Adrenergic receptors (alpha1A, alpha1B, alpha1D, and alpha2A), Histamine H1 and H2 receptors and Serotonin 5-HT2c, 5-HT5A, 5-HT6 receptors with high affinity. Dimebon may act by blocking NMDA receptors or voltage-gated Ca2+ channels and by preventing mitochondrial permeability pore transition.

Benidipine is an orally triple L-, T-, and N-type calcium channel blocker for the treatment of hypertension and angina pectoris synthesized and developed by Kyowa Hakko Kogyo Co., Ltd. Benidipine, approved in Japan in November 1991, has become one of the three best selling CCBs and is highly useful as a potent, long-lasting antihypertensive and antianginal agent.

Trimebutine [3,4,5-trimethoxybenzoic acid 2-(dimethylamino)-2-phenylbutylester] is a noncompetitive spasmolytic agent. The actions of trimebutine on the gastrointestinal tract are mediated via (i) an agonist effect on peripheral mu, kappa and delta opiate receptors and (ii) release of gastrointestinal peptides such as motilin and modulation of the release of other peptides, including vasoactive intestinal peptide, gastrin and glucagon. Trimebutine attenuated colonic motility mainly through the inhibition of L-type Ca(2+) channels at higher concentrations, whereas, at lower concentrations, it depolarized membrane potentials by reducing BK(ca) currents, resulting in the enhancement of the muscle contractions.Trimebutine accelerates gastric emptying, induces premature phase III of the migrating motor complex in the intestine and modulates the contractile activity of the colon. It is indicated for the treatment and relief of symptoms associated with the irritable bowel syndrome (spastic colon); and in postoperative paralytic ileus in order to accelerate the resumption of the intestinal transit following abdominal surgery.