Medifoxamine

Medifoxamine
Clinical data

Routes of administration	Oral
ATC code	N06AX13 (WHO)
Legal status
Legal status	℞ (Prescription only)
Pharmacokinetic data
Bioavailability	21%
Biological half-life	2.8 ± 1.04 hours (acute); 4.0 hours (chronic)
Identifiers
IUPAC name N,N-Dimethyl-2,2-diphenoxyethanamine
CAS Number	32359-34-5^Y
PubChem CID	36109
ChemSpider	33212
UNII	KWU7C2A1NT
KEGG	D07341^Y
ECHA InfoCard	100.046.359
Chemical and physical data
Formula	C₁₆H₁₉NO₂
Molar mass	257.328 g/mol
3D model (Jmol)	Interactive image
Chirality	Racemic mixture
SMILES CN(C)CC(OC1=CC=CC=C1)OC2=CC=CC=C2
InChI InChI=1S/C16H19NO2/c1-17(2)13-16(18-14-9-5-3-6-10-14)19-15-11-7-4-8-12-15/h3-12,16H,13H2,1-2H3 Key:QNMGHBMGNRQPNL-UHFFFAOYSA-N

Medifoxamine (INN) (brand names Clédial, Gerdaxyl) or medifoxamine fumarate, also known as N,N-dimethyl-2,2-diphenoxyethylamine, is an atypicalantidepressant with additional anxiolytic properties acting via dopaminergic and serotonergic mechanisms that was formerly marketed in France and Spain, as well as Morocco. The drug was first introduced in France sometime around 1990. It was withdrawn from the market in 1999 (Morocco) and 2000 (France) following incidences of hepatotoxicity.

Medifoxamine has been found to act preferentially as a relatively weak dopamine reuptake inhibitor, but also as an even weaker serotonin reuptake inhibitor (IC₅₀ = 1500 nM) and as a weak antagonist of the 5-HT_2A and 5-HT_2C receptors (IC₅₀ = 950 and 980, respectively; notably greater affinity relative to amitriptyline and imipramine). It is known to produce two active metabolites during first-pass metabolism in the liver, CRE-10086 (N-methyl-2,2-diphenoxyethylamine) and CRE-10357 (N,N-dimethyl-2-hydroxyphenoxy-2-phenoxyethylamine). The IC₅₀ values of CRE-10086 for serotonin transporter, 5-HT_2A, and 5-HT_2C binding are 450 nM, 330 nM, and 700 nM, respectively, while those of CRE-10357 are 660 nM, 1600 nM, and 6300 nM. Medifoxamine and its metabolites lack affinity for other serotonin receptors including 5-HT_1A, 5-HT_1B, 5-HT_1D, and 5-HT₃ (>10000 nM). As medifoxamine is metabolized extensively in the liver during first-pass metabolism, and as these metabolites have as much as 3-fold greater activity relative to medifoxamine, it is likely that they contribute significantly to the pharmacology of the parent drug.

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