Lomerizine
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Routes of administration | Oral |
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Lomerizine (
Solubility
Due to its lipophilic nature and small molecular size, lomerizine is able to cross the
Mechanism of action
Lomerizine works as a calcium antagonist
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
Lomerizine also shows neuroprotective effects against secondary degeneration resulting from injury in
While some calcium-channel blockers, such as
Medical use
Lomerizine is typically taken orally in a dose of 2 to 10 mg two to three times a day,[7] but doses of 20 mg are not uncommon.[9] 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.[10]
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.[9] Efficacies of 47% to 71% have been reported, and gender seems to have no effect on efficacy of the drug.
Lomerizine may cause drowsiness and flushing, but it lacks the serious cardiovascular effects and hypotension produced by other calcium antagonists. This is hypothesized to be due to the drug's selectivity for cerebral arteries[3] over peripheral arteries. No other side effects have been reported.
The acute toxicity for lomerizine in mice was found to be 44 mg/kg intravenously, 300 mg/kg orally, and over 1,200 mg/kg subcutaneously. Overdose can result in seizures or convulsions. The toxicity in humans has not been reported.[11]
Pharmacokinetics
Administered intravenously in rabbits at a dose of .03 mg/kg, the drug reached an average peak plasma concentration of 19.5 ± 6.5 ng/ml. This preparation had been completely metabolised within 60 minutes of administration.[10] When administered to rats at a dose of 5 mg/kg, lomerizine reached a Cmax of 27.6 ng/ML and Tmax of 90 minutes. In guinea pig and dog aortic membranes, the drug displaced the binding of calcium agonist 3H-Nitrendipine with an IC50 of 86 nM and a Ki of 340 nM.[12]
When administered orally to healthy male subjects in 10, 20, and 40 mg doses, lomerizine produced peak plasma levels of ≈ 7.3, 15.7, and 31.3 ng/ml.[10] In a group of 18 healthy adults, 10 mg of lomerizine administered orally had a half-life of 5.48 ± .90 hours, with a peak serum concentration (Cmax) of 9.06 ± 2.46 ng/mL. Tmax was reported as 2.72 ± .91 hours[13]
The IC50 for lomerizine is reported to be 2430.0 nM in humans.[14] The bioavailability of orally administered lomerizine is unaffected by gastric pH.[15]
References
- S2CID 39918828.
- .
- ^ PMID 14578410.
- ^ PMID 19474405.
- PMID 2850381.
- PMID 19783864.
- ^ PMID 15492768.
- ^ PMID 1405037.
- ^ PMID 17527044.
- ^ a b c US 6387910, Hara H, Shimazawa M, Iwakura Y, "Drug of improving optic nerve head circulation disorder", assigned to Merck Sharp and Dohme BV
- ^ "Material Safety Data Sheet for Lomerizine Dihydrochloride" (PDF). Chemblink. Sigma-Aldrich.
- ISBN 3764364351.
- PMID 24412691.
- PMID 17134896.
- ^ Nakada Y, Yokomachi H, Iwakura Y, Takahashi Y, Ozawa N (1999). "Effect of gastric acidity on the oral absorption of lomerizine hydrochloride". Yakuzaigaku. 59 (2): 84–88.