Identification

Name
Toloxatone
Accession Number
DB09245
Type
Small Molecule
Groups
Experimental
Description

Toloxatone is an antidepressant launched in 1984 in France for the treatment of depression. It acts as a selective and reversible inhibitor of monoamine oxidase-A (MOA) [5].

Structure
Thumb
Synonyms
Not Available
International/Other Brands
Humoryl (Sanofi Aventis)
Categories
UNII
5T206015T5
CAS number
29218-27-7
Weight
Average: 207.229
Monoisotopic: 207.089543283
Chemical Formula
C11H13NO3
InChI Key
MXUNKHLAEDCYJL-UHFFFAOYSA-N
InChI
InChI=1S/C11H13NO3/c1-8-3-2-4-9(5-8)12-6-10(7-13)15-11(12)14/h2-5,10,13H,6-7H2,1H3
IUPAC Name
5-(hydroxymethyl)-3-(3-methylphenyl)-1,3-oxazolidin-2-one
SMILES
CC1=CC(=CC=C1)N1CC(CO)OC1=O

Pharmacology

Indication

For the treatment of major depressive disorder.

Pharmacodynamics

This drug has been shown to help manage the symptoms of depression by maintaining neuro-synaptic levels of serotonin and catecholamines while regulating their metabolism, which leads to relief of depressive symptoms [1].

Mechanism of action

This medication is a reversible inhibitor of monoamine oxidase type-A (also known as RIMA).
MAO-A can be found in norepinephrinergic and serotonergic neurons and regulates the metabolism of serotonin and catecholamines, allowing for increased circulation in the synaptic cleft. Traditional monoamine oxidase inhibitors irreversibly inhibit monoamine oxidase and therefore, side effects, drug interactions, and food interactions persist as long as 2-3 weeks after discontinuing toloxatone. The elevation of serotonin and norepinephrine levels occurs rapidly after medication administration. However, the therapeutic relief of depressive symptoms requires weeks of daily treatment to observe results. Selective and reversible MAO-A inhibitors are more effective in treating major depression without several of the drug and food interactions associated with traditional monoamine oxidase inhibitors [6].

TargetActionsOrganism
UAmine oxidase [flavin-containing] A
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Mainly hepatic 1% of drug is excreted unchanged in the urine [3]

Half life

1-3 h [3]

Clearance

High hepatic excretion rate [3]

Toxicity

In rare cases, toloxatone toxicity may cause fulminant hepatitis [6]. More common adverse effects include dysuria, nausea, constipation, vertigo, and insomnia. Administration of toloxatone can lead to an increased risk of serotonin syndrome with selective serotonin reuptake inhibitors (SSRI), and tricyclic antidepressants [6]. Increased blood pressure can occur with sympathomimetic medication coadministration. One study showed that when combined with meals, elevated doses of toloxatone may contribute to elevated blood pressure in healthy subjects. This pharmacodynamic interaction could be explained by enhanced tyramine bioavailability in the presence of toloxatone. This tyramine in meals and toloxatone is unlikely to occur in patients after long-term administration of the drug at therapeutic dosages [2].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding and hemorrhage can be increased when Toloxatone is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding and hemorrhage can be increased when Toloxatone is combined with (S)-Warfarin.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidToloxatone may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazoleThe risk or severity of hypertension can be increased when 1-benzylimidazole is combined with Toloxatone.
2,4-thiazolidinedioneToloxatone may increase the hypoglycemic activities of 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamineToloxatone may increase the hypertensive activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineToloxatone may increase the hypertensive activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineToloxatone may increase the hypertensive activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineToloxatone may increase the hypertensive activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of bleeding and hemorrhage can be increased when Toloxatone is combined with 4-hydroxycoumarin.
Food Interactions
Not Available

References

General References
  1. Berlin I, Zimmer R, Thiede HM, Payan C, Hergueta T, Robin L, Puech AJ: Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase-A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects. Br J Clin Pharmacol. 1990 Dec;30(6):805-16. [PubMed:1705137]
  2. Provost JC, Funck-Brentano C, Rovei V, D'Estanque J, Ego D, Jaillon P: Pharmacokinetic and pharmacodynamic interaction between toloxatone, a new reversible monoamine oxidase-A inhibitor, and oral tyramine in healthy subjects. Clin Pharmacol Ther. 1992 Oct;52(4):384-93. [PubMed:1424410]
  3. Schoerlin MP, Guentert TW: [Pharmacokinetics and metabolism of reversible MAO-A inhibitors in the human]. Psychiatr Prax. 1989 Aug;16 Suppl 1:11-7. [PubMed:2685852]
  4. A reversible monoamine oxidase inhibitor, toloxatone: spectrophotometric and molecular orbital studies of the interaction with flavin adenine dinucleotide (FAD) [Link]
  5. Comparative investigation of the effect of moclobemide and toloxatone on monoamine oxidase activity and psychometric performance in healthy subjects [Link]
  6. Tolaxatone [Link]
  7. Chemistry [Link]
External Links
KEGG Drug
D02559
PubChem Compound
34521
PubChem Substance
310265148
ChemSpider
31769
BindingDB
50110725
ChEMBL
CHEMBL18116
Wikipedia
Toloxatone
ATC Codes
N06AG03 — Toloxatone

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
boiling point (°C)333[L1392]
water solubility1.22e-02 [L1392]
logP1.26[L1392]
Predicted Properties
PropertyValueSource
Water Solubility54.9 mg/mLALOGPS
logP0.61ALOGPS
logP1.41ChemAxon
logS-0.58ALOGPS
pKa (Strongest Acidic)14.61ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area49.77 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity54.7 m3·mol-1ChemAxon
Polarizability21.75 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as toluenes. These are compounds containing a benzene ring which bears a methane group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Toluenes
Direct Parent
Toluenes
Alternative Parents
Oxazolidinones / Carbamate esters / Organic carbonic acids and derivatives / Oxacyclic compounds / Azacyclic compounds / Primary alcohols / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Toluene / Oxazolidinone / Oxazolidine / Carbamic acid ester / Carbonic acid derivative / Organoheterocyclic compound / Azacycle / Oxacycle / Hydrocarbon derivative / Organic oxide
show 9 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin binding
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOA
Uniprot ID
P21397
Uniprot Name
Amine oxidase [flavin-containing] A
Molecular Weight
59681.27 Da
References
  1. Tolaxatone [Link]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serotonin binding
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOA
Uniprot ID
P21397
Uniprot Name
Amine oxidase [flavin-containing] A
Molecular Weight
59681.27 Da
References
  1. Tolaxatone [Link]

Drug created on October 23, 2015 16:16 / Updated on November 02, 2018 07:00