Clinical data | |
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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 |
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Pharmacokinetic data | |
Bioavailability | 21% [1] [2] |
Elimination half-life | 2.8 hours (acute);
[1]
[2] 4.0 hours (chronic) [3] |
Identifiers | |
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CAS Number |
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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 |
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(verify) |
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 [11] It was withdrawn from the market in 1999 (Morocco) and 2000 (France) following incidences of hepatotoxicity.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]
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-HT2A and 5-HT2C 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-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. [3] Medifoxamine and its metabolites lack affinity for other serotonin receptors including 5-HT1A, 5-HT1B, 5-HT1D, 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]
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]
Medifoxamine is the generic name of the drug and its INN while médifoxamine is its DCF . [6] [7] [8]
Medifoxamine was marketed under the brand names Clédial and Gerdaxyl. [6] [7]
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 |
|
Pharmacokinetic data | |
Bioavailability | 21% [1] [2] |
Elimination half-life | 2.8 hours (acute);
[1]
[2] 4.0 hours (chronic) [3] |
Identifiers | |
| |
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 |
| |
| |
(verify) |
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]
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-HT2A and 5-HT2C 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-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. [3] Medifoxamine and its metabolites lack affinity for other serotonin receptors including 5-HT1A, 5-HT1B, 5-HT1D, 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]
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]
Medifoxamine is the generic name of the drug and its INN while médifoxamine is its DCF . [6] [7] [8]
Medifoxamine was marketed under the brand names Clédial and Gerdaxyl. [6] [7]