Medifoxamine

Clinical data
Trade names	Clédial, Gerdaxyl
Synonyms	Medifoxamine fumarate; N,N-Dimethyl-2,2-diphenoxyethylamine
Routes of administration	By mouth
ATC code	N06AX13 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	21%[1][2]
Elimination half-life	2.8 hours (acute);[1][2] 4.0 hours (chronic)[3]
Identifiers
IUPAC name N,N-dimethyl-2,2-diphenoxyethanamine
CAS Number	32359-34-5 Y 16604-45-8 (fumarate) 16604-44-7 (picrate)
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 (JSmol)	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
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Medifoxamine, previously sold under the brand names Clédial and Gerdaxyl, is an atypical antidepressant^[4] with additional anxiolytic properties^[5] acting via dopaminergic and serotonergic mechanisms which was formerly marketed in France and Spain, as well as Morocco.^{[6][7][8][9][10]} The drug was first introduced in France sometime around 1990.^[11] It was withdrawn from the market in 1999 (Morocco) and 2000 (France) following incidences of hepatotoxicity.^[10][12][13]

Pharmacology[edit]

Pharmacodynamics[edit]

Medifoxamine has been found to act preferentially as a relatively weak dopamine reuptake inhibitor,^{[3][14][15][16]} but also as an even weaker serotonin reuptake inhibitor (IC₅₀ = 1,500 nM)^[3] 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).^[3][17][18] 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).^[3] 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, 1,600 nM, and 6,300  M.^[3] Medifoxamine and its metabolites lack affinity for other serotonin receptors including 5-HT_1A, 5-HT_1B, 5-HT_1D, and 5-HT₃ (>10,000 nM).^[3] 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.^[3]

Effectiveness and tolerability[edit]

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),^[3][14][19] 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).^[20] Studies in mice revealed that the drug does not possess any sedative or locomotor stimulant effects.^[3] 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.^[3]Double-blind controlled clinical studies have found it to have similar effectiveness to imipramine, clomipramine, and maprotiline in the treatment of depression.^{[3][9][18][19]}

Society and culture[edit]

Generic names[edit]

Medifoxamine is the generic name of the drug and its INN while médifoxamine is its DCF.^[6][7][8]

Brand names[edit]

Medifoxamine was marketed under the brand names Clédial and Gerdaxyl.^[6][7]

References[edit]