Mexazolam
Benzodiazepam
From Wikipedia, the free encyclopedia
Mexazolam[1] (marketed under the trade names Melex and Sedoxil)[2] is a drug which is a benzodiazepine derivative.[3] Mexazolam has been trialed for anxiety and was found to be effective in alleviating anxiety at one week follow-up. Mexazolam is metabolised via the CYP3A4 pathway. HMG-CoA reductase inhibitors including simvastatin, simvastatin acid, lovastatin, fluvastatin, atorvastatin and cerivastatin inhibit the metabolism of mexazolam,[4] but not the HMG-CoA reductase inhibitor pravastatin.[5][6] Its principal active metabolites are chlorodesmethyldiazepam (also known as chloronordiazepam or delorazepam, trade name Dadumir) and chloroxazepam (also known as lorazepam, trade name Ativan).[7] Researchers have found a dose of 1.67 mg mexazolam equals 5 mg diazepam.[8] Clinical studies suggest that 3 mg of mexazolam has a comparable effect to 1.5 mg of alprazolam.[9]
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| Trade names | Melex, Sedoxil |
| Other names | 13-chloro- 2-(2-chlorophenyl)- 5-methyl- 3-oxa- 6,9-diazatricyclo[8.4.0.02,6] tetradeca- 1(10),11,13-trien- 8-one |
| AHFS/Drugs.com | International Drug Names |
| Routes of administration | Oral |
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| Metabolism | Liver (CYP3A4) |
| Excretion | Kidney |
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| Formula | C18H16Cl2N2O2 |
| Molar mass | 363.24 g·mol−1 |
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Pharmacokinetics
Mexazolam is a long-acting benzodiazepine that undergoes extensive hepatic metabolism. In humans, the parent drug is primarily oxidized by cytochrome P450 3A isoforms, yielding two active benzodiazepine metabolites: chloronordiazepam and chloroxazepam. Mexazolam follows biphasic elimination profile: the initial distribution phase has a half-life of approximately 1.4 hours, reflecting rapid tissue uptake and first-pass metabolism, following by a terminal phase with a half-life of about 76 hours. The long duration of the terminal phase driven by high plasma protein binding (over 90 percent) and gradual release from peripheral compartments.[10] The active metabolites further extend duration of action of the drug.[10][11] The elimination half-lives of the active metabolites is 130–200 h, which supports once-daily dosing but also calls for caution regarding accumulation and residual sedative effects during prolonged therapy.[10]
Mechanism of action
Mexazolam's primary target is GABAA receptor, benzodiazepine site, via the active metabolite chloronordiazepam.[11] Mexazolam potentiates GABA currents at α2/α3 (anxiolytic) subunit‑containing receptors. The drug has minimal effect on α1 (sedative) amplitude;[12][11] as such, mexazolam has lower sedative load compared to classical benzodiazepines[11] such as chlordiazepoxide.[13]