Esmirtazapine

Legal statusLegal status Pharmacokinetic dataMetabolismLiver (CYP2D6)^[2]Elimination half-life10 hours^[1]IdentifiersCAS NumberPubChem CIDDrugBankChemSpiderUNIIKEGGECHA InfoCard100.056.994 Chemical and physical dataFormulaC₁₇H₁₉N₃Molar mass265.360 g·mol⁻¹3D model (JSmol)Melting point114 to 116 °C (237 to 241 °F)Solubility in waterSoluble in methanol and chloroform  ^NY (what is this?)  (verify)

Esmirtazapine (ORG-50,081) is a tetracyclic antidepressant drug that was under development by Organon for the treatment of insomnia and vasomotor symptoms (e.g., hot flashes) associated with menopause.^[3][4][5][6] Esmirtazapine is the (S)-(+)-enantiomer of mirtazapine and possesses similar overall pharmacology, including inverse agonist actions at H₁ and 5-HT₂ receptors and antagonist actions at α₂-adrenergic receptors.^[3][7]

Notably, esmirtazapine has a shorter half life of around 10 hours, compared to R-mirtazapine and racemic mixture, which has a half-life of 18–40 hours.^[1] Merck has run several studies on low dose (3–4.5 mg) esmirtazapine for the treatment of insomnia. It is attractive for treating insomnia since it is a potent H₁-inhibitor and a 5-HT_2A antagonist.^[8][1] Unlike low-dose mirtazapine, the half life (10 hours) is short enough that next-day sedation may be manageable, however, for people with CYP2D6 polymorphisms, which constitute a sizable fraction of the population, the half-life is expected to be quite a bit longer. Merck researchers claimed that the incidence of next-day sedation was not a problem in one of their studies, but this claim has been challenged (15% of patients complained of daytime sleepiness vs 3.5% in the placebo group).^[9]

In March 2010, Merck terminated its internal clinical development program for esmirtazapine for hot flashes and insomnia, "for strategic reasons".^[10]

See also

• Cidoxepin

References

External links

• Media related to Esmirtazapine at Wikimedia Commons