Identification

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Name
Methimazole
Accession Number
DB00763  (APRD00002)
Type
Small Molecule
Groups
Approved
Description

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 inappropriate18,19.

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.

Structure
Thumb
Synonyms
  • 1-Methylimidazole-2(3H)-thione
  • Methimazole
  • Thiamazol
  • Thiamazole
  • Thiamazolum
  • Tiamazol
External IDs
NSC 38608 / USAF el-30
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MethimazoleTablet10 mg/1OralUnited Research Laboratories, Inc.2006-04-19Not applicableUs
MethimazoleTablet5 mg/1OralUnited Research Laboratories, Inc.2006-04-19Not applicableUs
Methimazole Tablets USPTabletOralEndo Ventures LtdNot applicableNot applicableCanada
Methimazole Tablets USPTabletOralEndo Ventures LtdNot applicableNot applicableCanada
Methimazole Tablets USPTabletOralEndo Ventures LtdNot applicableNot applicableCanada
TapazoleTablet20 mgOralPaladin Labs IncNot applicableNot applicableCanada
TapazoleTablet10 mgOralPaladin Labs Inc2008-01-07Not applicableCanada
Tapazole 5mg TabletTabletOralPaladin Labs Inc1951-12-31Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-methimazoleTabletOralApotex Corporation2005-03-18Not applicableCanada
Dom-methimazoleTabletOralDominion PharmacalNot applicableNot applicableCanada
Jamp MethimazoleTabletOralJamp Pharma CorporationNot applicableNot applicableCanada
Jamp MethimazoleTabletOralJamp Pharma CorporationNot applicableNot applicableCanada
Mar-methimazoleTabletOralMarcan Pharmaceuticals Inc2018-10-19Not applicableCanada
Mar-methimazoleTabletOralMarcan Pharmaceuticals Inc2018-10-19Not applicableCanada
MethimazoleTablet10 mg/1OralBoca Pharmacal, Inc.2012-03-072017-02-28Us
MethimazoleTablet5 mg/1OralAmerican Health Packaging2010-03-022019-11-30Us
MethimazoleTablet10 mg/1OralRebel Distributors2010-07-07Not applicableUs49884 0641 01 nlmimage10 dd08eec7
MethimazoleTablet10 mg/1OralDispensing Solutions, Inc.2012-01-16Not applicableUs23155 0071 01 nlmimage10 423ca135
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

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International/Other Brands
Danantizol (Gador S.A.) / Favistan (Temmler) / Metizol (ICN) / Strumazol (Organon) / Strumazole / Thacapzol (Recip) / Thycapzol (Sandoz) / Thyrozol (Merck) / Tirozol (Merck)
Categories
UNII
554Z48XN5E
CAS number
60-56-0
Weight
Average: 114.169
Monoisotopic: 114.025168892
Chemical Formula
C4H6N2S
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

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

Associated Conditions
Pharmacodynamics

Methimazole inhibits the synthesis of thyroid hormones resulting in an alleviation of hyperthyroidism.18,19 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

TargetActionsOrganism
AThyroid peroxidase
substrate
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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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

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

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

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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
(R)-warfarinMethimazole may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinMethimazole may decrease the anticoagulant activities of (S)-Warfarin.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Methimazole is combined with 2-Methoxyethanol.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Methimazole.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Methimazole.
3-[4-(1-formylpiperazin-4-yl)-benzylidenyl]-2-indolinoneThe therapeutic efficacy of Methimazole can be decreased when used in combination with SU4984.
3-isobutyl-1-methyl-7H-xanthineMethimazole may decrease the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a higher serum level.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Methimazole.
4-hydroxycoumarinMethimazole may decrease the anticoagulant activities of 4-hydroxycoumarin.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Methimazole.
Additional Data Available
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    Extended Description

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  • Severity
    Severity

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  • Evidence Level
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Food Interactions
  • Always take at the same moment in regard to meals, food may affect absorption unpredictably.

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
  1. 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. [PubMed:4042519]
  2. 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. [PubMed:6546390]
  3. 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. [PubMed:3830069]
  4. 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. [PubMed:27615550]
  5. 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. [PubMed:7356900]
  6. 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. [PubMed:30320502]
  7. 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. [PubMed:25789213]
  8. 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. [PubMed:10725113]
  9. 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. [PubMed:9172960]
  10. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  11. Clark SM, Saade GR, Snodgrass WR, Hankins GD: Pharmacokinetics and pharmacotherapy of thionamides in pregnancy. Ther Drug Monit. 2006 Aug;28(4):477-83. [PubMed:16885714]
  12. 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. [PubMed:23883148]
  13. 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. [PubMed:28153798]
  14. Cooper DS: Antithyroid drugs. N Engl J Med. 2005 Mar 3;352(9):905-17. doi: 10.1056/NEJMra042972. [PubMed:15745981]
  15. 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. [PubMed:24622372]
  16. 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. [PubMed:24980470]
  17. CaymenChem: Methimazole MSDS [Link]
  18. FDA Approved Drugs: Methimazole [Link]
  19. 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
ChEBI
50673
ChEMBL
CHEMBL1515
Therapeutic Targets Database
DNC001429
PharmGKB
PA450422
HET
MMZ
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Methimazole
ATC Codes
H03BB52 — Thiamazole, combinationsH03BB02 — Thiamazole
AHFS Codes
  • 68:36.08 — Antithyroid Agents
PDB Entries
2gvc / 5ff1 / 5gsn

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentGraves´ Disease / Thyroid Associated Ophthalmopathy1
2CompletedTreatmentDermatomyositis / Polymyositis1
2TerminatedSupportive CareGlioblastoma Multiforme (GBM)1
3RecruitingTreatmentGraves Diseases / Graves Ophthalmopathy / Graves' Ophthalmopathy Worsened1
4CompletedPreventionGraves´ Disease1
4CompletedTreatmentGraves Diseases / Toxic Nodular Goitre1
4CompletedTreatmentGraves' Disease1
4CompletedTreatmentGraves' Disease / Toxic Nodular Goitre1
4Unknown StatusDiagnosticHealthy Volunteers1
Not AvailableActive Not RecruitingNot AvailableHyperthyroidism1
Not AvailableCompletedNot AvailableGraves Diseases1
Not AvailableCompletedTreatmentGraves Diseases1
Not AvailableCompletedTreatmentGraves' Disease1
Not AvailableRecruitingNot AvailableGut Microbiota1
Not AvailableRecruitingNot AvailableHyperthyroidism1
Not AvailableRecruitingNot AvailableMicrobiota2
Not AvailableTerminatedTreatmentGraves Ophthalmopathy1

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
FormRouteStrength
TabletOral10 mg/1
TabletOral5 mg/1
TabletOral10 mg
TabletOral20 mg
TabletOral
Prices
Unit descriptionCostUnit
Methimazole powder9.49USD g
Methimazole 20 mg tablet1.9USD tablet
Tapazole 10 mg tablet1.45USD tablet
Northyx 20 mg tablet0.94USD tablet
Northyx 15 mg tablet0.82USD tablet
Methimazole 10 mg tablet0.78USD tablet
Tapazole 5 mg tablet0.66USD tablet
Northyx 10 mg tablet0.47USD tablet
Methimazole 5 mg tablet0.45USD tablet
Northyx 5 mg tablet0.29USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)143-146 °CDPD Label (Canada)
water solubilityFreely solubleDPD Label (Canada)
Predicted Properties
PropertyValueSource
Water Solubility11.3 mg/mLALOGPS
logP-0.38ALOGPS
logP0.75ChemAxon
logS-1ALOGPS
pKa (Strongest Acidic)10.41ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area15.27 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity33.23 m3·mol-1ChemAxon
Polarizability11.64 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9156
Blood Brain Barrier+0.9731
Caco-2 permeable+0.6156
P-glycoprotein substrateNon-substrate0.8213
P-glycoprotein inhibitor INon-inhibitor0.7552
P-glycoprotein inhibitor IINon-inhibitor0.944
Renal organic cation transporterNon-inhibitor0.7662
CYP450 2C9 substrateNon-substrate0.7919
CYP450 2D6 substrateNon-substrate0.8985
CYP450 3A4 substrateNon-substrate0.7849
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7105
Ames testNon AMES toxic0.8582
CarcinogenicityNon-carcinogens0.9348
BiodegradationNot ready biodegradable0.9815
Rat acute toxicity1.8215 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9401
hERG inhibition (predictor II)Non-inhibitor0.8416
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.12 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0900000000-810e7a010dd805f3251d
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-5900000000-e88140069cbfa61f9c51
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-3969b3a3102e9214d562
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0900000000-3e543dd0166f52789fcd
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0900-9300000000-90c58541a936c6fdd275
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-9000000000-9a1c61f319838c2ebce9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-066r-8900000000-9230df83b87c13377bfb
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0900000000-275f9771b8d1d7486052
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0900000000-1763fdc1a812fa765250
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0900000000-78877e6d65fda61a0e67
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-1900000000-c979e7cdbceb656b6a1e
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-1900000000-1447e5774eda5dc3fe26
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-066r-9300000000-41d253a513ee17fed774
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-9000000000-11684a341cebaa28c427
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a60-9000000000-7637560408e70990bc27

Taxonomy

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
N-substituted imidazole / Imidazole-2-thione / Heteroaromatic compound / Imidazole / Azole / Thiourea / Azacycle / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazoles, thioureas (CHEBI:50673) / a small molecule (CPD-11282)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
Inhibitor
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
  1. 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. [PubMed:10365684]
  2. 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. [PubMed:11241400]
  3. 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. [PubMed:12755690]
  4. 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. [PubMed:1320313]
  5. Chiovato L, Pinchera A: The microsomal/peroxidase antigen: modulation of its expression in thyroid cells. Autoimmunity. 1991;10(4):319-31. [PubMed:1663395]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. 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. [PubMed:30320502]

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
  1. 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. [PubMed:9172960]
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
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  2. 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. [PubMed:9172960]
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
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  2. 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. [PubMed:9172960]
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
  1. 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. [PubMed:9172960]
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
  1. 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. [PubMed:9172960]
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
  1. 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. [PubMed:9172960]
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
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  2. 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. [PubMed:9172960]
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
  1. 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. [PubMed:9172960]
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
  1. 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. [PubMed:25789213]

Drug created on June 13, 2005 07:24 / Updated on December 06, 2019 11:49