Medifoxamine


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 It was withdrawn from the market in 1999 and 2000 following incidences of hepatotoxicity.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 and as a weak antagonist of the 5-HT2A and 5-HT2C receptors. It is known to produce two active metabolites during first-pass metabolism in the liver, CRE-10086 and CRE-10357. 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. 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, and is also apparently inactive as a norepinephrine reuptake inhibitor. 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 while médifoxamine is its.

Brand names

Medifoxamine was marketed under the brand names Clédial and Gerdaxyl.