Methimazole
Identification
- Summary
Methimazole is a thionamide antithyroid agent that inhibits the actions of thyroid peroxidase, leading to a reduction in thyroid hormone synthesis and amelioration of hyperthyroidism.
- Brand Names
- Tapazole
- Generic Name
- Methimazole
- DrugBank Accession Number
- DB00763
- Background
Methimazole is a thionamide antithyroid agent that inhibits the synthesis of thyroid hormones.6,14,12 It was first introduced as an antithyroid agent in 19492 and is now commonly used in the management of hyperthyroidism, particularly in those for whom more aggressive options such as surgery or radioactive iodine therapy are inappropriate.18,19
On a weight basis, methimazole is 10 times more potent than the other major antithyroid thionamide used in North America, propylthiouracil,19 and is the active metabolite of the pro-drug carbimazole, which is an antithyroid medication used in the United Kingdom and parts of the former British Commonwealth.14 Traditionally, methimazole has been preferentially used over propylthiouracil due to the risk of fulminant hepatotoxicity carried by the latter,15 with propylthiouracil being preferred in pregnancy due to a perceived lower risk of teratogenic effects. Despite documented teratogenic effects in its published labels,18,19 the true teratogenicity of methimazole appears to be unclear11,15,16 and its place in therapy may change in the future.
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 114.169
Monoisotopic: 114.025168892 - Chemical Formula
- C4H6N2S
- Synonyms
- 1-Methylimidazole-2(3H)-thione
- Methimazole
- Thiamazol
- Thiamazole
- Thiamazolum
- Tiamazol
- External IDs
- NSC 38608
- USAF el-30
Pharmacology
- Indication
In the United States, methimazole is indicated for the treatment of hyperthyroidism in patients with Graves' disease or toxic multinodular goiter for whom thyroidectomy or radioactive iodine therapy are not appropriate treatment options. Methimazole is also indicated for the amelioration of hyperthyroid symptoms in preparation for thyroidectomy or radioactive iodine therapy.18
In Canada, methimazole carries the above indications and is also indicated for the medical treatment of hyperthyroidism regardless of other available treatment options.19
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Graves' disease •••••••••••• ••• • ••••••••• ••• ••••••• •• ••••••••••• •••••• ••••••• Treatment of Hyperthyroidism •••••••••••• Symptomatic treatment of Hyperthyroidism •••••••••••• Treatment of Toxic multinodular goiter •••••••••••• ••• • ••••••••• ••• ••••••• •• ••••••••••• •••••• ••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Methimazole inhibits the synthesis of thyroid hormones resulting in an alleviation of hyperthyroidism.1819 Onset of action occurs within 12 to 18 hours, and its duration of action is 36 to 72 hours, likely due to concentration of methimazole and some metabolites within the thyroid gland after administration.11
The most serious potential side effect of methimazole therapy is agranulocytosis, and patients should be instructed to monitor for, and report, any signs or symptoms of agranulocytosis such as fever or sore throat. Other cytopenias may also occur during methimazole therapy. There also exists the potential for severe hepatic toxicity with the use of methimazole, and monitoring for signs and symptoms of hepatic dysfunction, such as jaundice, anorexia, pruritus, and elevation in liver transaminases, is prudent in patients using this therapy.18,19
- Mechanism of action
Methimazole's primary mechanism of action appears to be interference in an early step in thyroid hormone synthesis involving thyroid peroxidase (TPO), however the exact method through which methimazole inhibits this step is unclear.6 TPO, along with hydrogen peroxide, normally catalyzes the conversion of iodide to iodine and then further catalyzes the incorporation of this iodine onto the 3 and/or 5 positions of the phenol rings of tyrosine residues in thyroglobulin. These thyroglobulin molecules then degrade within thyroid follicular cells to form either thyroxine (T4) or tri-iodothyronine (T3), which are the main hormones produced by the thyroid gland.13
Methimazole may directly inhibit TPO, but has been shown in vivo to instead act as a competitive substrate for TPO, thus becoming iodinated itself and interfering with the iodination of thyroglobulin.6 Another proposed theory is that methimazole’s sulfur moiety may interact directly with the iron atom at the centre of TPO’s heme molecule, thus inhibiting its ability to iodinate tyrosine residues.12 Other proposed mechanisms with weaker evidence include methimazole binding directly to thyroglobulin or direct inhibition of thyroglobulin itself.6
Target Actions Organism AThyroid peroxidase substrateinhibitorHumans - Absorption
Absorption of methimazole after oral administration is rapid and extensive,3,5,1 with an absolute bioavailability of approximately 0.931 and a Tmax ranging from 0.25 to 4.0 hours.3,1 Cmax is slightly, but not significantly, higher in hyperthyroid patients, and both Cmax and AUC are significantly affected by the oral dose administered.3
- Volume of distribution
The apparent volume of distribution of methimazole has been reported as roughly 20 L.5 Following oral administration, methimazole is highly concentrated in the thyroid gland - intrathyroidal methimazole levels are approximately 2 to 5 times higher than peak plasma levels, and remain high for 20 hours after ingestion.6
- Protein binding
Methimazole exhibits little-to-no protein binding, existing primarily as free drug in the serum.4,5,11
- Metabolism
Methimazole is rapidly and extensively metabolized by the liver, mainly via the CYP450 and FMO enzyme systems.7,8 Several metabolites have been identified, though the specific enzyme isoforms responsible for their formation are not entirely clear. One of the first methimazole metabolites identified, 3-methyl-2-thiohydantoin, may contribute to antithyroid activity - its antithyroid activity has been demonstrated in rats and may explain the prolonged duration of iodination inhibition following administration despite methimazole's relatively short half-life.5
A number of metabolites have been investigated as being the culprits behind methimazole-induced hepatotoxicity. Both glyoxal and N-methylthiourea have established cytotoxicity and are known metabolic products of methimazole's dihydrodiol intermediate. Sulfenic and sulfinic acid derivatives of methimazole are thought to be the ultimate toxicants responsible for hepatotoxicity, though their origin is unclear - they may arise from direct oxidation of methimazole via FMO, or from oxidation of N-methylthiourea further downstream in the metabolic process.7,8
Hover over products below to view reaction partners
- Route of elimination
Urinary excretion of unchanged methimazole has been reported to be between 7% and 12%. Elimination via feces appears to be limited, with a cumulative fecal excretion of 3% after administration of methimazole.3 Enterohepatic circulation also appears to play a role in the elimination of methimazole and its metabolites, as significant amounts of these substances are found in the bile post-administration.11
- Half-life
Following a single intravenous bolus injection of 10mg of methimazole, the t1/2 of the distribution phase was 0.17 hours and the t1/2 of the elimination phase was 5.3 hours.1 Methimazole's primary active metabolite, 3-methyl-2-thiohydantoin, has a half-life approximately 3 times longer than its parent drug.5 Renal impairment does not appear to alter the half-life of methimazole, but patients with hepatic impairment showed an increase in half-life roughly proportional to the severity of their impairment - moderate insufficiency resulted in a elimination t1/2 of 7.1 hours, while severe insufficiency resulted in an elimination t1/2 of 22.1 hours.1
There does not appear to be any significant differences in half-life based on thyroid status (i.e. no difference between euthyroid and hyperthyroid patients).1,2,3
- Clearance
Following a single intravenous bolus injection of 10mg of methimazole, clearance was found to be 5.70 L/h.1 Renal impairment does not appear to alter clearance of methimazole, but patients with hepatic impairment showed a reduction in clearance roughly proportional to the severity of their impairment - moderate insufficiency resulted in a clearance of 3.49 L/h, while severe insufficiency resulted in a clearance of 0.83 L/h.1
There does not appear to be any significant differences in clearance based on thyroid status (i.e. no difference between euthyroid and hyperthyroid patients).1,2,3
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
The oral LD50 of methimazole in rats is 2250 mg/kg.17 Signs and symptoms of methimazole overdose may include gastrointestinal distress, headache, fever, joint pain, pruritus, and edema. More serious adverse effects, such as aplastic anemia or agranulocytosis, may manifest within hours to days.18,19 Hepatitis, nephrotic syndrome, exfoliative dermatitis, and CNS effects such as neuropathy or CNS depression/stimulation are also potential, albeit less frequent, results of overdose.18,19
Management of overdose involves supportive treatment as dictated by the patient's status.18,19 This may involve monitoring of the patient's vital signs, blood gases, serum electrolytes, or bone marrow function as indicated.19
- 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 metabolism of 1,2-Benzodiazepine can be decreased when combined with Methimazole. Abacavir Methimazole may decrease the excretion rate of Abacavir which could result in a higher serum level. Abatacept The risk or severity of adverse effects can be increased when Methimazole is combined with Abatacept. Abciximab Methimazole may increase the anticoagulant activities of Abciximab. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Methimazole. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Images
- International/Other Brands
- Danantizol (Gador S.A.) / Favistan (Temmler) / Metizol (ICN) / Strumazol (Organon) / Strumazole / Thacapzol (Recip) / Thycapzol (Sandoz) / Thyrozol (Merck) / Tirozol (Merck)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Methimazole Tablet 10 mg/1 Oral United Research Laboratories, Inc. 2006-04-19 Not applicable US Methimazole Tablet 5 mg/1 Oral United Research Laboratories, Inc. 2006-04-19 Not applicable US Methimazole Tablets USP Tablet 5 mg Oral Endo Ventures Ltd. Not applicable Not applicable Canada Methimazole Tablets USP Tablet 20 mg Oral Endo Ventures Ltd. Not applicable Not applicable Canada Methimazole Tablets USP Tablet 10 mg Oral Endo Ventures Ltd. Not applicable Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-methimazole Tablet 5 mg Oral Apotex Corporation 2005-03-18 Not applicable Canada Dom-methimazole Tablet 5 mg Oral Dominion Pharmacal Not applicable Not applicable Canada Jamp Methimazole Tablet 10 mg Oral Jamp Pharma Corporation 2021-08-21 Not applicable Canada Jamp Methimazole Tablet 5 mg Oral Jamp Pharma Corporation 2020-08-21 Not applicable Canada Mar-methimazole Tablet 5 mg Oral Marcan Pharmaceuticals Inc 2018-10-19 Not applicable Canada
Categories
- ATC Codes
- H03BB52 — Thiamazole, combinations
- H03BB — Sulfur-containing imidazole derivatives
- H03B — ANTITHYROID PREPARATIONS
- H03 — THYROID THERAPY
- H — SYSTEMIC HORMONAL PREPARATIONS, EXCL. SEX HORMONES AND INSULINS
- Drug Categories
- Antithyroid agents
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2A6 Inhibitors
- Cytochrome P-450 CYP2A6 Inhibitors (weak)
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strong)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (weak)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strong)
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inhibitors
- Drugs that are Mainly Renally Excreted
- Hormone Antagonists
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Imidazoles
- Immunosuppressive Agents
- Myelosuppressive Agents
- Sulfur Compounds
- Sulfur-Containing Imidazole Derivatives
- Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins
- Thyroid Hormone Synthesis Inhibitor
- Thyroid Hormone Synthesis Inhibitors
- Thyroid Products
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as imidazolethiones. These are aromatic compounds containing an imidazole ring which bears a thioketone group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Azolines
- Sub Class
- Imidazolines
- Direct Parent
- Imidazolethiones
- Alternative Parents
- N-substituted imidazoles / Heteroaromatic compounds / Thioureas / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Hydrocarbon derivatives
- Substituents
- Aromatic heteromonocyclic compound / Azacycle / Azole / Heteroaromatic compound / Hydrocarbon derivative / Imidazole / Imidazole-2-thione / N-substituted imidazole / Organic nitrogen compound / Organonitrogen compound
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- imidazoles, thioureas (CHEBI:50673) / a small molecule (CPD-11282)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 554Z48XN5E
- CAS number
- 60-56-0
- InChI Key
- PMRYVIKBURPHAH-UHFFFAOYSA-N
- InChI
- InChI=1S/C4H6N2S/c1-6-3-2-5-4(6)7/h2-3H,1H3,(H,5,7)
- IUPAC Name
- 1-methyl-2,3-dihydro-1H-imidazole-2-thione
- SMILES
- CN1C=CNC1=S
References
- Synthesis Reference
李光文李剑平倪国成, "Methimazole synthesizing and purifying method." Chinese Patent CN107162983A, published September, 2017.
- General References
- Jansson R, Lindstrom B, Dahlberg PA: Pharmacokinetic properties and bioavailability of methimazole. Clin Pharmacokinet. 1985 Sep-Oct;10(5):443-50. doi: 10.2165/00003088-198510050-00006. [Article]
- Cooper DS, Bode HH, Nath B, Saxe V, Maloof F, Ridgway EC: Methimazole pharmacology in man: studies using a newly developed radioimmunoassay for methimazole. J Clin Endocrinol Metab. 1984 Mar;58(3):473-9. doi: 10.1210/jcem-58-3-473. [Article]
- Okamura Y, Shigemasa C, Tatsuhara T: Pharmacokinetics of methimazole in normal subjects and hyperthyroid patients. Endocrinol Jpn. 1986 Oct;33(5):605-15. doi: 10.1507/endocrj1954.33.605. [Article]
- Okosieme OE, Lazarus JH: Current trends in antithyroid drug treatment of Graves' disease. Expert Opin Pharmacother. 2016 Oct;17(15):2005-17. doi: 10.1080/14656566.2016.1232388. Epub 2016 Sep 14. [Article]
- Skellern GG, Knight BI, Low CK, Alexander WD, McLarty DG, Kalk WJ: The pharmacokinetics of methimazole after oral administration of carbimazole and methimazole, in hyperthyroid patients. Br J Clin Pharmacol. 1980 Feb;9(2):137-43. doi: 10.1111/j.1365-2125.1980.tb05823.x. [Article]
- Burch HB, Cooper DS: ANNIVERSARY REVIEW: Antithyroid drug therapy: 70 years later Eur J Endocrinol. 2018 Oct 12;179(5):R261-R274. doi: 10.1530/EJE-18-0678. [Article]
- Heidari R, Niknahad H, Jamshidzadeh A, Eghbal MA, Abdoli N: An overview on the proposed mechanisms of antithyroid drugs-induced liver injury. Adv Pharm Bull. 2015 Mar;5(1):1-11. doi: 10.5681/apb.2015.001. Epub 2015 Mar 5. [Article]
- Mizutani T, Yoshida K, Murakami M, Shirai M, Kawazoe S: Evidence for the involvement of N-methylthiourea, a ring cleavage metabolite, in the hepatotoxicity of methimazole in glutathione-depleted mice: structure-toxicity and metabolic studies. Chem Res Toxicol. 2000 Mar;13(3):170-6. [Article]
- Guo Z, Raeissi S, White RB, Stevens JC: Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997 Mar;25(3):390-3. [Article]
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Clark SM, Saade GR, Snodgrass WR, Hankins GD: Pharmacokinetics and pharmacotherapy of thionamides in pregnancy. Ther Drug Monit. 2006 Aug;28(4):477-83. [Article]
- Manna D, Roy G, Mugesh G: Antithyroid drugs and their analogues: synthesis, structure, and mechanism of action. Acc Chem Res. 2013 Nov 19;46(11):2706-15. doi: 10.1021/ar4001229. Epub 2013 Jul 24. [Article]
- Carvalho DP, Dupuy C: Thyroid hormone biosynthesis and release. Mol Cell Endocrinol. 2017 Dec 15;458:6-15. doi: 10.1016/j.mce.2017.01.038. Epub 2017 Jan 31. [Article]
- Cooper DS: Antithyroid drugs. N Engl J Med. 2005 Mar 3;352(9):905-17. doi: 10.1056/NEJMra042972. [Article]
- Cooper DS, Laurberg P: Hyperthyroidism in pregnancy. Lancet Diabetes Endocrinol. 2013 Nov;1(3):238-49. doi: 10.1016/S2213-8587(13)70086-X. Epub 2013 Oct 18. [Article]
- Mallela MK, Strobl M, Poulsen RR, Wendler CC, Booth CJ, Rivkees SA: Evaluation of developmental toxicity of propylthiouracil and methimazole. Birth Defects Res B Dev Reprod Toxicol. 2014 Aug;101(4):300-7. doi: 10.1002/bdrb.21113. Epub 2014 Jun 30. [Article]
- CaymenChem: Methimazole MSDS [Link]
- FDA Approved Drug Products: TAPAZOLE (methimazole) oral tablet [Link]
- DPD Approved Drugs: Methimazole [Link]
- External Links
- Human Metabolome Database
- HMDB0014901
- KEGG Drug
- D00401
- KEGG Compound
- C07190
- PubChem Compound
- 1349907
- PubChem Substance
- 46506536
- ChemSpider
- 1131173
- BindingDB
- 50241361
- 6835
- ChEBI
- 50673
- ChEMBL
- CHEMBL1515
- ZINC
- ZINC000001187543
- Therapeutic Targets Database
- DNC001429
- PharmGKB
- PA450422
- PDBe Ligand
- MMZ
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Thiamazole
- PDB Entries
- 2gvc / 5ff1 / 5gsn
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 4 Completed Prevention Graves´ Disease 1 4 Completed Treatment Graves' Disease 1 4 Completed Treatment Graves' Disease / Toxic Nodular Goitre 2 4 Recruiting Treatment Drug Relapse / Drug Withdrawal Symptoms / Graves' Disease / Treatments 1 4 Unknown Status Diagnostic Healthy Subjects (HS) 1
Pharmacoeconomics
- Manufacturers
- Actavis totowa llc
- Caraco pharmaceutical laboratories ltd
- Cedar pharmaceuticals llc
- Mylan pharmaceuticals inc
- Sandoz inc
- King pharmaceuticals inc
- King pharmaceuticals research and development inc sub king pharmaceuticals inc
- Packagers
- AAIPharma Inc.
- Actavis Group
- Amerisource Health Services Corp.
- Caraco Pharmaceutical Labs
- Cedar Pharmaceuticals LLC
- Centrix Pharmaceuticals
- Dispensing Solutions
- Eon Labs
- Heartland Repack Services LLC
- Kaiser Foundation Hospital
- King Pharmaceuticals Inc.
- Medisca Inc.
- Mikart Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Nucare Pharmaceuticals Inc.
- Par Pharmaceuticals
- Philopharm GmbH
- Physicians Total Care Inc.
- Remedy Repack
- Resource Optimization and Innovation LLC
- Southwood Pharmaceuticals
- United Research Laboratories Inc.
- Vangard Labs Inc.
- Dosage Forms
Form Route Strength Tablet Oral 10 mg/1 Tablet Oral 5 mg/1 Tablet Oral 10.000 mg Tablet Oral 10 mg Tablet Oral 20 mg Tablet, film coated Oral 20 MG Tablet, film coated Oral 5 MG Tablet, film coated Oral 10 Mg Tablet Oral 5.000 mg Tablet Oral Tablet, film coated Oral Tablet Oral 5 mg - Prices
Unit description Cost Unit Methimazole powder 9.49USD g Methimazole 20 mg tablet 1.9USD tablet Tapazole 10 mg tablet 1.45USD tablet Northyx 20 mg tablet 0.94USD tablet Northyx 15 mg tablet 0.82USD tablet Methimazole 10 mg tablet 0.78USD tablet Tapazole 5 mg tablet 0.66USD tablet Northyx 10 mg tablet 0.47USD tablet Methimazole 5 mg tablet 0.45USD tablet Northyx 5 mg tablet 0.29USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 143-146 °C DPD Label (Canada) water solubility Freely soluble DPD Label (Canada) - Predicted Properties
Property Value Source Water Solubility 11.3 mg/mL ALOGPS logP -0.38 ALOGPS logP 0.75 Chemaxon logS -1 ALOGPS pKa (Strongest Acidic) 10.41 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 0 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 15.27 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 33.23 m3·mol-1 Chemaxon Polarizability 11.64 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9156 Blood Brain Barrier + 0.9731 Caco-2 permeable + 0.6156 P-glycoprotein substrate Non-substrate 0.8213 P-glycoprotein inhibitor I Non-inhibitor 0.7552 P-glycoprotein inhibitor II Non-inhibitor 0.944 Renal organic cation transporter Non-inhibitor 0.7662 CYP450 2C9 substrate Non-substrate 0.7919 CYP450 2D6 substrate Non-substrate 0.8985 CYP450 3A4 substrate Non-substrate 0.7849 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9232 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7105 Ames test Non AMES toxic 0.8582 Carcinogenicity Non-carcinogens 0.9348 Biodegradation Not ready biodegradable 0.9815 Rat acute toxicity 1.8215 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9401 hERG inhibition (predictor II) Non-inhibitor 0.8416
Spectra
- Mass Spec (NIST)
- Download (8.12 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 113.947035 predictedDarkChem Lite v0.1.0 [M-H]- 113.940135 predictedDarkChem Lite v0.1.0 [M-H]- 113.852935 predictedDarkChem Lite v0.1.0 [M-H]- 121.80206 predictedDeepCCS 1.0 (2019) [M+H]+ 115.061335 predictedDarkChem Lite v0.1.0 [M+H]+ 115.034235 predictedDarkChem Lite v0.1.0 [M+H]+ 114.982635 predictedDarkChem Lite v0.1.0 [M+H]+ 123.73746 predictedDeepCCS 1.0 (2019) [M+Na]+ 114.355235 predictedDarkChem Lite v0.1.0 [M+Na]+ 114.340035 predictedDarkChem Lite v0.1.0 [M+Na]+ 114.253835 predictedDarkChem Lite v0.1.0 [M+Na]+ 131.78075 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- SubstrateInhibitor
- General Function
- Peroxidase activity
- Specific Function
- Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).
- Gene Name
- TPO
- Uniprot ID
- P07202
- Uniprot Name
- Thyroid peroxidase
- Molecular Weight
- 102961.63 Da
References
- Sugawara M, Sugawara Y, Wen K: Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles. Thyroid. 1999 May;9(5):513-8. [Article]
- Manzon RG, Holmes JA, Youson JH: Variable effects of goitrogens in inducing precocious metamorphosis in sea lampreys (Petromyzon marinus). J Exp Zool. 2001 Apr 15;289(5):290-303. [Article]
- Ferreira AC, de Carvalho Cardoso L, Rosenthal D, de Carvalho DP: Thyroid Ca2+/NADPH-dependent H2O2 generation is partially inhibited by propylthiouracil and methimazole. Eur J Biochem. 2003 Jun;270(11):2363-8. [Article]
- Magnusson RP, Yu B, Brennan V: Effect of serum thyrotropin levels on the concentration of messenger RNA for thyroid peroxidase in the rat. Acta Endocrinol (Copenh). 1992 May;126(5):460-6. [Article]
- Chiovato L, Pinchera A: The microsomal/peroxidase antigen: modulation of its expression in thyroid cells. Autoimmunity. 1991;10(4):319-31. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Burch HB, Cooper DS: ANNIVERSARY REVIEW: Antithyroid drug therapy: 70 years later Eur J Endocrinol. 2018 Oct 12;179(5):R261-R274. doi: 10.1530/EJE-18-0678. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Supporting data are limited to in vitro studies.
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Guo Z, Raeissi S, White RB, Stevens JC: Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997 Mar;25(3):390-3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
- Gene Name
- CYP2A6
- Uniprot ID
- P11509
- Uniprot Name
- Cytochrome P450 2A6
- Molecular Weight
- 56501.005 Da
References
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Guo Z, Raeissi S, White RB, Stevens JC: Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997 Mar;25(3):390-3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Guo Z, Raeissi S, White RB, Stevens JC: Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997 Mar;25(3):390-3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Current data supporting this enzyme inhibition is limited to one in vitro study.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Guo Z, Raeissi S, White RB, Stevens JC: Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997 Mar;25(3):390-3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Data supporting this enzyme action are limited to the findings of 1 in vitro study.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Guo Z, Raeissi S, White RB, Stevens JC: Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997 Mar;25(3):390-3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Guo Z, Raeissi S, White RB, Stevens JC: Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997 Mar;25(3):390-3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Guo Z, Raeissi S, White RB, Stevens JC: Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997 Mar;25(3):390-3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Guo Z, Raeissi S, White RB, Stevens JC: Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997 Mar;25(3):390-3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Trimethylamine monooxygenase activity
- Specific Function
- Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an impor...
- Gene Name
- FMO3
- Uniprot ID
- P31513
- Uniprot Name
- Dimethylaniline monooxygenase [N-oxide-forming] 3
- Molecular Weight
- 60032.975 Da
References
- Heidari R, Niknahad H, Jamshidzadeh A, Eghbal MA, Abdoli N: An overview on the proposed mechanisms of antithyroid drugs-induced liver injury. Adv Pharm Bull. 2015 Mar;5(1):1-11. doi: 10.5681/apb.2015.001. Epub 2015 Mar 5. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55