Levomilnacipran

Levomilnacipran

Systematic (IUPAC) name
(1S,2R)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide
Clinical data
Trade names	Fetzima
Pregnancy category	US: C (Risk not ruled out)
Legal status	℞ (Prescription only)
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	92%
Protein binding	22%
Metabolism	Hepatic (primarily by CYP3A4)
Biological half-life	12 hours
Excretion	Renal
Identifiers
CAS Number	96847-55-1 Y 175131-60-9 (hydrochloride)
ATC code	none
PubChem	CID: 6917779
IUPHAR/BPS	7435
ChemSpider	5293005 N
UNII	UGM0326TXX Y
KEGG	D10072 N
Chemical data
Formula	C15H22N2O
Molecular mass	246.348 g/mol
SMILES CCN(CC)C(=O)[C@]1(C[C@H]1CN)C2=CC=CC=C2
InChI InChI=1S/C15H22N2O/c1-3-17(4-2)14(18)15(10-13(15)11-16)12-8-6-5-7-9-12/h5-9,13H,3-4,10-11,16H2,1-2H3/t13-,15+/m0/s1 N Key:GJJFMKBJSRMPLA-DZGCQCFKSA-N N
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Levomilnacipran (brand name Fetzima) is an antidepressant approved for the treatment of major depressive disorder in the United States. It was developed by Forest Laboratories and Pierre Fabre Group, and was approved by the Food and Drug Administration in July 2013. Levomilnacipran is the levo- enantiomer of milnacipran, and has similar effects and pharmacology, acting as a serotonin-norepinephrine reuptake inhibitor (SNRI).

The FDA approved levomilnacipran in July 2013 based on the results of one 10-week phase II and four 8-week phase III clinical trials. Four of the five trials demonstrated a statistically significant superiority to placebo as measured by the Montgomery–Åsberg Depression Rating Scale. Superiority to placebo was also demonstrated by improvement in the Sheehan Disability Scale. Side effects seen more often than with placebo included nausea, dizziness, sweating, constipation, insomnia, increased heart rate and blood pressure, urinary hesitancy, erectile dysfunction and delayed ejaculation in males, vomiting, tachycardia, and palpitations.

Relative to other SNRIs, levomilnacipran, as well as milnacipran, differ in that they are much more balanced reuptake inhibitors of serotonin and norepinephrine. To demonstrate, the serotonin:norepinephrine ratios of SNRIs are as follows: venlafaxine = 30:1, duloxetine = 10:1, desvenlafaxine = 10:1, milnacipran = 1:3, and levomilnacipran = 1:2. The clinical implications of more balanced elevations of serotonin and norepinephrine are unclear, but may include improved effectiveness, though also increased side effects.

Levomilnacipran has recently been found to act as an inhibitor of beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), which is responsible for β-amyloid plaque formation, and hence may be a potentially useful drug in the treatment of Alzheimer's disease.