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Antidepressant
Medifoxamine
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Medifoxamine

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Medifoxamine
Medifoxamine.svg
Clinical data
Trade names Clédial, Gerdaxyl
Other names Medifoxamine fumarate; N,N-Dimethyl-2,2-diphenoxyethylamine
Routes of
administration		 By mouth
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 21%
Elimination half-life 2.8 hours (acute);
4.0 hours (chronic)
Identifiers
  • N,N-dimethyl-2,2-diphenoxyethanamine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard 100.046.359
Chemical and physical data
Formula C16H19NO2
Molar mass 257.333 g·mol−1
3D model (JSmol)
Chirality Racemic mixture
  • CN(C)CC(OC1=CC=CC=C1)OC2=CC=CC=C2
  • 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
  (verify)

Medifoxamine, previously sold under the brand names Clédial and Gerdaxyl, is an atypical antidepressant with additional anxiolytic properties acting via dopaminergic and serotonergic mechanisms which 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 It was withdrawn from the market in 1999 (Morocco) and 2000 (France) following incidences of hepatotoxicity.

Pharmacology

Pharmacodynamics

Medifoxamine has been found to act preferentially as a relatively weak dopamine reuptake inhibitor, but also as an even weaker serotonin reuptake inhibitor (IC50 = 1,500 nM) and as a weak antagonist of the 5-HT2A and 5-HT2C 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-HT2A, and 5-HT2C binding are 450 nM, 330 nM, and 700 nM, respectively, while those of CRE-10357 are 660 nM, 1,600 nM, and 6,300  M. Medifoxamine and its metabolites lack affinity for other serotonin receptors including 5-HT1A, 5-HT1B, 5-HT1D, and 5-HT3 (>10,000 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.

Effectiveness and tolerability

Unlike many tricyclic antidepressants, medifoxamine lacks anticholinergic and alpha blocker properties (very low affinity for the muscarinic acetylcholine receptors and 10-fold lower affinity for the α1-adrenergic receptor relative to 5-HT2 binding sites), and is also apparently inactive as a norepinephrine reuptake inhibitor (although the same source stating this also states that it is inactive as a serotonin reuptake inhibitor, which was subsequently found not to be the case). Studies in mice revealed that the drug does not possess any sedative or locomotor stimulant effects. In accordance with all of the preceding, medifoxamine was found to be well tolerated at dosages of 100–300 mg per day in clinical trials.Double-blind controlled clinical studies have found it to have similar effectiveness to imipramine, clomipramine, and maprotiline in the treatment of depression.

Society and culture

Generic names

Medifoxamine is the generic name of the drug and its INN while médifoxamine is its DCF.

Brand names

Medifoxamine was marketed under the brand names Clédial and Gerdaxyl.


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