Ethosuximide is a succinimide anticonvulsant, used in the treatment of epilepsy. Ethosuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli. Binds to T-type voltage sensitive calcium channels. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Ethosuximide is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.

Mesuximide (or methsuximide) is an anticonvulsant medication. It is sold by Pfizer under the name Petinutin. Binds to T-type voltage sensitive calcium channels. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Mesuximide is used for the control of absence (petit mal) seizures that are refractory to other drugs.

Dimethadione (5,5-dimethyl-2,4-oxazolidinedione) is the N-demethylated metabolite of the anticonvulsant trimethadione. Dimethadione is considered to be a blocker of T-type calcium channel. Dimethadione also inhibits a specific potassium channel (Ikr) in HERG-transfected cells. It exerts teratogenic effect especially congenital heart defects. Dimethadione can be used for the measurement of regional tissue pH using positron emission tomography.

Paramethadione is an anticonvulsant in the oxazolidinedione class developed by the Abbott Laboratories, approved by the Food and Drug Administration in 1949 for the treatment of absence seizures, also called partial seizures. Paramethadione acts to reduce T-type calcium currents in thalamic neurons which has been proposed to underlie the 3-Hz spike-and-wave discharge seen on electroencephalogram (EEG) during absence seizures.

Trimethadione (brand name is TRIDIONE) is an oxazolidinedione compound that was developed as an antiepileptic agent for control of petit mal seizures that are refractory to treatment with other drugs. Tridione does not modify the maximal seizure pattern in patients undergoing electroconvulsive therapy and has a sedative effect that may increase to the point of ataxia when excessive doses are used. Trimethadione acts as a voltage-activated T-type Ca2+ channel blocker. Trimethadione is rapidly absorbed from the gastrointestinal tract. It is demethylated by liver microsomes to the active metabolite, dimethadione. Approximately 3% of a daily dose of tridione is recovered in the urine as the unchanged drug. The majority of trimethadione is excreted slowly by the kidney in the form of dimethadione.

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.

Carisbamate is an experimental anticonvulsant drug that was under development by Johnson & Johnson Pharmaceutical Research and Development but never marketed. Acute and chronic nonclinical toxicological studies have not revealed any significant abnormalities other than dose-related CNS toxicity. Carisbamate displays high potency in a broad range of rodent seizure and epilepsy models at doses well below those that produce CNS toxicity. The exact mechanism of action is unknown but neuroprotective and antiseizure activity of Carisbamate likely results in part from decreased calcium accumulation through blockade of T-type Ca2+ channels. A phase II clinical trial in the treatment of partial seizures demonstrated that the compound has efficacy in the treatment of partial seizures and a good safety profile. In large multicenter phase III clinical trial for the treatment of partial seizures carisbamate at doses of 300, 800, and 1,600 mg/d was effective as adjunctive therapy for reducing the frequency of partial-onset seizures. The most common adverse events, encountered mainly at daily doses of 1000 mg or more, were CNS-related, including headache, dizziness, somnolence, and nausea. In another phase III clinical trial, carisbamate was not more efficacious in migraine prophylaxis than placebo, but carisbamate monotherapy was well tolerated at doses up to 600 mg per day. Johnson & Johnson received provisional approval by the FDA to market carisbamate under the brand name of Comfyde. However, on August 21, 2009, Johnson & Johnson reported that the FDA had failed to give marketing approval.

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.

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.

Niflumic acid belongs to the group of nonsteroidal anti-inflammatory drugs (NSAIDs) and used in the treatment of rheumatoid arthritis, and joint and muscular pain. Its mechanism of action is believed to be based on selective inhibition of cycloxygenases-2 that results in antipyretic, analgesic, and anti-inflammatory effects. In addition to these effects on prostaglandin synthesis, it has been shown to act as a positive allosteric modulator on α1β2γ2 and as a negative modulator on α6β2 and α6β2γ2 (and α1β2) GABAA receptors. In addition, was reported, that niflumic acid blocked T-type calcium channels. It is available for clinical use in several European countries.