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]
Clinical data | |
---|---|
Routes of administration | Oral |
ATC code |
|
Legal status | |
Legal status |
|
Pharmacokinetic data | |
Metabolism | Liver (CYP2D6)[2] |
Elimination half-life | 10 hours[1] |
Identifiers | |
| |
CAS Number |
|
PubChem CID |
|
DrugBank |
|
ChemSpider |
|
UNII |
|
KEGG |
|
ECHA InfoCard | 100.056.994 |
Chemical and physical data | |
Formula | C17H19N3 |
Molar mass | 265.360 g·mol−1 |
3D model (JSmol) |
|
Melting point | 114 to 116 °C (237 to 241 °F) |
Solubility in water | Soluble in methanol and chloroform |
| |
| |
(what is this?) (verify) |
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-HT2A 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]