Lomerizine (INN; trade name Migsis) is a diphenylpiperazine class L-type and T-type calcium channel blocker. This drug is currently used clinically for the treatment of migraines, while also being used experimentally for the treatment of glaucoma and optic nerve injury.

Due to its lipophilic nature and small molecular size, lomerizine is able to cross the blood brain barrier. For delivery in aqueous systems, nanoparticle therapy may be used. Along with lipids, lomerizine is soluble in chloroform, methanol, and DMSO.

Lomerizine works as a calcium antagonist by blocking voltage-dependent calcium channels. A study using [³H]Nitrendipine showed that lomerizine allosterically inhibits binding in calcium channels at a different site from the 1,4 dihydropyridine binding site. However, its antimigraine effects are believed to be due not to the blocking of calcium channels, but to the antagonizing effects of lomerizine on the 5HT_2A receptor. The drug was shown to competitively inhibit binding of [³H]spiperone to 5-HT_2A receptors, inhibiting the 5-HT driven release of Ca²⁺. Lomerizine treatment of 5-HT_2A expressing cells led to the inhibition of Ca²⁺ release in response to 5-HT, while Ca²⁺ release in response to ATP was unaffected. By preventing the release of Ca²⁺, lomerizine prevents serotonin-induced contraction of the basilar artery, which can lead to migraines.

Lomerizine has also been shown to possess neuroprotective effects, specifically in the case of retinal damage. Doses of .03 mg/kg given intravenously as a pretreatment were shown to prevent glutamate-induced neurotoxicity, while also providing protection against NMDA-induced and kainate-induced neurotoxicity. Lomerizine was shown to have little affinity for NMDA or kainate receptors, so its protectivity against neurotoxicity in these cases is believed to be due to the blocking of Ca²⁺ influx through voltage-dependent calcium channels. By blocking these channels and preventing Ca²⁺ release, lomerizine increases circulation in the optic nerve head. These effects show that lomerizine may prove to be a useful treatment for ischemic retinal diseases, such as glaucoma.

Lomerizine also shows neuroprotective effects against secondary degeneration resulting from injury in retinal ganglion cells. In this case, increased membrane depolarization, in conjunction with the inability of the sodium-calcium exchanger to function due to depleted ATP stores, causes the activation of calcium-dependent signal transduction. These processes lead to cell death through either apoptosis or necrosis. Lomerizine's role in blocking Ca²⁺ can rescue these cells from death by preventing excitotoxicity. Decreased intracellular calcium also prevents necrosis by decreasing permeability, and apoptotic death is reduced through the reduction of calcium-dependent apoptotic agents.

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.

Lomerizine is typically taken orally in a dose of 2 to 10 mg two to three times a day, but doses of 20 mg are not uncommon. It is also available in an intravenous solution of lomerizine hydrochloride, but the preferred route of administration, especially for treatment of the optic nerve, is oral.

In a clinical study, long-term lomerizine usage was shown to be both safe and effective in the treatment of migraines. However, efficacy of the drug decreases with age, with a significant correlation between age and efficacy at preventing migraine attacks. Efficacies of 47% to 71% have been reported, and gender seems to have no effect on efficacy of the drug.