NAV

Toloxatone

Identification

Generic Name
Toloxatone
DrugBank Accession Number
DB09245
Background

Toloxatone is an antidepressant agent, the first ever use of which was in France, 1984. It acts as a selective and reversible inhibitor of monoamine oxidase-A (MOA) 5.

Type
Small Molecule
Groups
Experimental
Structure
3D
Similar Structures
Weight
Average: 207.229
Monoisotopic: 207.089543283
Chemical Formula
C11H13NO3
Synonyms
  • Toloxatone
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Pharmacology

Indication

For the treatment of major depressive disorder.

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Contraindications & Blackbox Warnings
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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
Humans
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

Adverse Effects
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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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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1,2-BenzodiazepineThe risk or severity of CNS depression can be increased when Toloxatone is combined with 1,2-Benzodiazepine.
AbacavirAbacavir may decrease the excretion rate of Toloxatone which could result in a higher serum level.
AbaloparatideToloxatone may increase the orthostatic hypotensive activities of Abaloparatide.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Toloxatone is combined with Abciximab.
AcarboseToloxatone may increase the hypoglycemic activities of Acarbose.
Food Interactions
Not Available

Products

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International/Other Brands
Humoryl (Sanofi Aventis)

Categories

ATC Codes
N06AG03 — Toloxatone
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Alcohol / Aromatic heteromonocyclic compound / Azacycle / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide / Organic oxygen compound
show 9 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
5T206015T5
CAS number
29218-27-7
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

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. [Article]
  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. [Article]
  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. [Article]
  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]
KEGG Drug
D02559
PubChem Compound
34521
PubChem Substance
310265148
ChemSpider
31769
BindingDB
50110725
RxNav
38382
ChEMBL
CHEMBL18116
Wikipedia
Toloxatone

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount

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-MSsplash10-066r-1900000000-efa501f1ba81606b621e
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0190000000-36105332d5cdeeae4e88
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4l-0950000000-c56ca1d7483db0bcd268
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a59-1960000000-a7f90f5afbb84f35f3dd
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-2900000000-116e4e808009b81580dc
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0ac3-6900000000-8b8dc9761201fc9c85d3
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9400000000-822b146c672469a66efd
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-147.32332
predicted
DeepCCS 1.0 (2019)
[M+H]+151.15065
predicted
DeepCCS 1.0 (2019)
[M+Na]+160.3796
predicted
DeepCCS 1.0 (2019)

Targets

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Details1. Amine oxidase [flavin-containing] A
Kind
Protein
Organism
Humans
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

Details1. Amine oxidase [flavin-containing] A
Kind
Protein
Organism
Humans
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 at October 23, 2015 22:16 / Updated at February 21, 2021 18:52