Esmirtazapine

Esmirtazapine

Clinical data
Routes of administration	Oral
ATC code	none
Legal status
Legal status	In general: uncontrolled
Pharmacokinetic data
Metabolism	Liver (CYP2D6)
Elimination half-life	10 hours
Identifiers
IUPAC name (S)-1,2,3,4,10,14b-hexahydro-2-methylpyrazino(2,1-a)pyrido(2,3-c)(2)benzazepine
CAS Number	61337-87-9 Y
PubChem CID	3085218 E. maleate: 6451144
DrugBank	DB06678 N
ChemSpider	2342166 Y
UNII	4685R51V7M
KEGG	D04055 Y
ECHA InfoCard	100.056.994
Chemical and physical data
Formula	C17H19N3
Molar mass	265.360 g·mol−1
3D model (JSmol)	Interactive image
Melting point	114 to 116 °C (237 to 241 °F)
Solubility in water	Soluble in methanol and chloroform mg/mL (20 °C)
SMILES CN1CCN2c3c(cccn3)Cc4ccccc4[C@H]2C1
InChI InChI=1S/C17H19N3/c1-19-9-10-20-16(12-19)15-7-3-2-5-13(15)11-14-6-4-8-18-17(14)20/h2-8,16H,9-12H2,1H3/t16-/m1/s1 Y Key:RONZAEMNMFQXRA-MRXNPFEDSA-N Y
NY (what is this?)  (verify)

Esmirtazapine (ORG-50,081) is a tetracyclic antidepressant drug which was under development by Organon for the treatment of insomnia and vasomotor symptoms (e.g., hot flashes) associated with menopause. 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.

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. 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. 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).

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

See also

• Cidoxepin

External links

• Media related to Esmirtazapine at Wikimedia Commons