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
- Weight
- Average: 207.229
Monoisotopic: 207.089543283 - Chemical Formula
- C11H13NO3
- Synonyms
- Toloxatone
Pharmacology
- Indication
For the treatment of major depressive disorder.
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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.Target Actions Organism UAmine oxidase [flavin-containing] A antagonistHumans - 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Toloxatone is combined with 1,2-Benzodiazepine. Abacavir Abacavir may decrease the excretion rate of Toloxatone which could result in a higher serum level. Abaloparatide Toloxatone may increase the orthostatic hypotensive activities of Abaloparatide. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Toloxatone is combined with Abciximab. Acarbose Toloxatone 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
- Agents that produce hypertension
- Agents that reduce seizure threshold
- Antidepressive Agents
- Central Nervous System Agents
- Central Nervous System Depressants
- Drugs that are Mainly Renally Excreted
- Enzyme Inhibitors
- Monoamine Oxidase A Inhibitors
- Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates
- Monoamine Oxidase Inhibitors
- Nervous System
- Oxazoles
- Psychoanaleptics
- Psychotropic Drugs
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- 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
- 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]
- 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]
- 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]
- A reversible monoamine oxidase inhibitor, toloxatone: spectrophotometric and molecular orbital studies of the interaction with flavin adenine dinucleotide (FAD) [Link]
- Comparative investigation of the effect of moclobemide and toloxatone on monoamine oxidase activity and psychometric performance in healthy subjects [Link]
- Tolaxatone [Link]
- Chemistry [Link]
- External Links
- KEGG Drug
- D02559
- PubChem Compound
- 34521
- PubChem Substance
- 310265148
- ChemSpider
- 31769
- BindingDB
- 50110725
- 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);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source boiling point (°C) 333 [L1392] water solubility 1.22e-02 [L1392] logP 1.26 [L1392] - Predicted Properties
Property Value Source Water Solubility 54.9 mg/mL ALOGPS logP 0.61 ALOGPS logP 1.41 Chemaxon logS -0.58 ALOGPS pKa (Strongest Acidic) 14.61 Chemaxon pKa (Strongest Basic) -1.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 49.77 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 54.7 m3·mol-1 Chemaxon Polarizability 21.75 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-066r-1900000000-efa501f1ba81606b621e Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-0190000000-36105332d5cdeeae4e88 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4l-0950000000-c56ca1d7483db0bcd268 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0a59-1960000000-a7f90f5afbb84f35f3dd Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-2900000000-116e4e808009b81580dc Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0ac3-6900000000-8b8dc9761201fc9c85d3 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9400000000-822b146c672469a66efd Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 147.32332 predictedDeepCCS 1.0 (2019) [M+H]+ 151.15065 predictedDeepCCS 1.0 (2019) [M+Na]+ 160.3796 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- 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
- Tolaxatone [Link]
Enzymes
- 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
- Tolaxatone [Link]
Drug created at October 23, 2015 22:16 / Updated at February 21, 2021 18:52