METHIMAZOLE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C4H6N2S
Molecular Weight	114.169
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C=CNC1=S

InChI

InChIKey=PMRYVIKBURPHAH-UHFFFAOYSA-N

InChI=1S/C4H6N2S/c1-6-3-2-5-4(6)7/h2-3H,1H3,(H,5,7)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00763
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/cdi/methimazole.html

Methimazole (also known as Tapazole or Thiamazole or MMI) is an antithyroid drug. Methimazole binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (T4) and tri-iodothyronine (T3), which are the main hormones produced by the thyroid gland. So methimazole effectively inhibits the production of new thyroid hormones. Methimazole is used for the treatment of hyperthyroidism, goiter, Graves disease and psoriasis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thyroid peroxidase 8 Target ID: CHEMBL1839 Sources: http://www.drugbank.ca/drugs/DB00763	Inhibitor 8228

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyperthyroidism 13 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040320s005lbl.pdf	Primary		Approved 8360	Tapazole Approved Use TAPAZOLE is indicated: In patients with Graves’ disease with hyperthyroidism or toxic multinodular goiter for whom surgery or radioactive iodine therapy is not an appropriate treatment option. To ameliorate symptoms of hyperthyroidism in preparation for thyroidectomy or radioactive iodine therapy. Launch Date -6.1646399E11

C_max

Value	Dose	Analyte	Population
248 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4042519/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
213 ng/mL EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.17 mg/kg bw single, oral dose: 0.17 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
299 ng/mL EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.21 mg/kg bw single, oral dose: 0.21 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
380 ng/mL EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.3 mg/kg bw single, oral dose: 0.3 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
803 ng/mL EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.57 mg/kg bw single, oral dose: 0.57 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Analyte	Population
1661 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4042519/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2657 ng × h/mL EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.17 mg/kg bw single, oral dose: 0.17 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
3228 ng × h/mL EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.21 mg/kg bw single, oral dose: 0.21 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
4773 ng × h/mL EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.3 mg/kg bw single, oral dose: 0.3 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
7136 ng × h/mL EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.57 mg/kg bw single, oral dose: 0.57 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1833 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4042519/	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	METHIMAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2450 ng × h/mL EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.16 mg/kg bw single, intravenous dose: 0.16 mg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
2922 ng × h/mL EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.21 mg/kg bw single, intravenous dose: 0.21 mg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
5.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4042519/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
14 h EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.17 mg/kg bw single, oral dose: 0.17 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
14 h EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.21 mg/kg bw single, oral dose: 0.21 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
20.1 h EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.3 mg/kg bw single, oral dose: 0.3 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
15 h EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.57 mg/kg bw single, oral dose: 0.57 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
5.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4042519/	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	METHIMAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
20.7 h EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.16 mg/kg bw single, intravenous dose: 0.16 mg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
18.5 h EXPERIMENT https://www.jstage.jst.go.jp/article/endocrj1954/33/5/33_5_605/_pdf	0.21 mg/kg bw single, intravenous dose: 0.21 mg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered:	METHIMAZOLE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579	inhibitor 1752	inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCTN1 29 CYP2E1 876 CYP1A2 1509 CYP2C19 1463 CYP2A6 704 CYP2B6 799

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1909	inhibitor 3240 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	major [IC50 14 uM]
CYP2A6 736	inhibitor 3240 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	no [IC50 >/=1000 uM]
CYP2C19 1537	inhibitor 3240 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	no [IC50 >/=1000 uM]
CYP2D6 1875	inhibitor 3240 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	no [IC50 >/=1000 uM]
CYP2E1 964	inhibitor 3240 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	no [IC50 >/=1000 uM]
CYP2B6 985	inhibitor 3240 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	weak [IC50 100 uM]
CYP2C9 1803	inhibitor 3240 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	weak [IC50 100 uM]
CYP1A2 1673	inhibitor 3240 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	weak [Inhibition 50 uM]
OCTN1 29	inhibitor 3240 Sources: http://transportal.compbio.ucsf.edu/compounds/methimazole/	weak [Ki 7500 uM]

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:50673	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50673
ChemicalBook	CB9220870	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9220870
MolPort	MolPort-000-563-838	https://www.molport.com/shop/molecule-link/MolPort-000-563-838
MolPort	MolPort-002-508-019	https://www.molport.com/shop/molecule-link/MolPort-002-508-019
Selleck Chemicals	Methimazole(Tapazole)	http://www.selleckchem.com/products/Methimazole(Tapazole).html
ZINC	ZINC000001187543	http://zinc15.docking.org/substances/ZINC000001187543
eMolecules	1971965	https://www.emolecules.com/cgi-bin/more?vid=1971965
eMolecules	496094	https://www.emolecules.com/cgi-bin/more?vid=496094

PubMed

Title	Date	PubMed
Body, heart, thyroid gland and skeletal muscle weight changes in rats with altered thyroid status.	2001	11829324
Drug-induced congenital defects: strategies to reduce the incidence.	2001	11735646
[Ablative therapy for immune hyperthyroidism in patients with ophthalmopathy].	2001	11593892
The activity of antioxidant enzymes and the content of uncoupling protein-1 in the brown adipose tissue of hypothyroid rats: comparison with effects of iopanoic acid.	2001	11521740
Identification of the gene encoding Brain Cell Membrane Protein 1 (BCMP1), a putative four-transmembrane protein distantly related to the Peripheral Myelin Protein 22 / Epithelial Membrane Proteins and the Claudins.	2001	11472633
Coexistence of Graves' disease and struma ovarii: case report and literature review.	2001 Apr	11456276
Malignant hyperthermia in a patient with Graves' disease during subtotal thyroidectomy.	2001 Apr	11456272
Morning granulocytopenia in a case of Graves' disease.	2001 Apr	11456265
A case of pulmonary metastatic thyroid cancer complicated with Graves' disease.	2001 Apr	11456264
Graves' disease presenting as elephantiasic pretibial myxedema and nodules of the hands.	2001 Apr	11454085
[Simultaneous occurrence of Basedow's disease and autoimmune hemolytic anemia].	2001 Apr	11400305
Estimation of antithyroid drug dose in Graves' disease: value of quantification of thyroid blood flow with color duplex sonography.	2001 Aug	11527601
Remission and recurrence of hyperthyroid Graves' disease during and after methimazole treatment when assessed by IgE and interleukin 13.	2001 Aug	11502776
The effect of methimazole pretreatment on the efficacy of radioactive iodine therapy in Graves' hyperthyroidism: one-year follow-up of a prospective, randomized study.	2001 Aug	11502768
Clinical practice. Subclinical hyperthyroidism.	2001 Aug 16	11519506
Protracted expression of serotonin transporter and altered thalamocortical projections in the barrelfield of hypothyroid rats.	2001 Dec	11860492
Impact of hyperthyroidism and its correction on vascular reactivity in humans.	2001 Dec 18	11748103
The systolic function of the left ventricle of the heart in patients with hyperthyroidism during therapy.	2001 Feb	11505747
Antioxidants in the treatment of Graves disease.	2001 Feb	11463161
Effects of thyroid hormones on cardiac structure: a tissue characterization study in patients with thyroid disorders before and after treatment.	2001 Jul	11484889
Cloning, sequencing, tissue distribution, and heterologous expression of rat flavin-containing monooxygenase 3.	2001 Jul 1	11414682
Interplay of pregnancy, lactation, and hyperthyroidism leading to severe osteoporosis in a young woman.	2001 Jul-Aug	11497477
A case of thyrotoxicosis with pancytopenia.	2001 Jun	11523911
Cross-bridge and calcium behavior in ferret papillary muscle in different thyroid states.	2001 Jun	11492956
Serum levels of cytokines in children and adolescents with Graves' disease and non-toxic nodular goiter.	2001 Jun	11453524
Influence of hypothyroid state on 45Ca(2+) influx and sensitivity of rat uterus to nifedipine and diltiazem.	2001 Jun 15	11516438
[Effect of thyroxine upon prevention of recurrence of Graves' disease treated with antithyroid drugs].	2001 Mar 10	11798886
[Efficacy of quinagolide in the treatment of a patient with hypophyseal resistance to thyroid hormones].	2001 May	11496561
Bronchial asthma induced by an antithyroid drug.	2001 May	11348974
Method for the analysis of thyreostats in meat tissue using gas chromatography with nitrogen phosphorus detection and tandem mass spectrometric confirmation.	2001 May	11348029
Methimazole-induced pulmonary hemorrhage associated with antimyeloperoxidase-antineutrophil cytoplasmic antibody: a case report.	2001 Nov	11802538
Different role of insulin in GLUT-1 and -4 regulation in heart and skeletal muscle during perinatal hypothyroidism.	2001 Nov	11595665
Apoptosis, necrosis, and cell proliferation induced by S-(1,2-dichlorovinyl)-L-cysteine in primary cultures of human proximal tubular cells.	2001 Nov 15	11708895
Risk of torsades de pointes from oral erythromycin with concomitant carbimazole (methimazole) administration.	2001 Oct	11707056
Suppression of serum TSH by Graves' Ig: evidence for a functional pituitary TSH receptor.	2001 Oct	11600546
Use of oral cholecystographic agents in the treatment of amiodarone-induced hyperthyroidism.	2001 Oct	11600529
Thyroid hormone-deficient period prior to the onset of hearing is associated with reduced levels of beta-tectorin protein in the tectorial membrane: implication for hearing loss.	2001 Oct 19	11489885
Thyroid hormone regulates oxidative phosphorylation in the cerebral cortex and striatum of neonatal rats.	2001 Sep	11553679
Ca(2+)/nicotinamide adenine dinucleotide phosphate-dependent H(2)O(2) generation is inhibited by iodide in human thyroids.	2001 Sep	11549671
Neonatal hyperthyroidism in infants of mothers previously thyroidectomized due to Graves' disease.	2001 Sep-Oct	11592578
Severe embryopathy and exposure to methimazole in early pregnancy.	2002 Feb	11836348
Cell necrosis and apoptosis are differentially regulated during goitre development and iodine-induced involution.	2002 Feb	11834455
Influence of hypothyroidism on circulating concentrations and liver expression of IGF-binding proteins mRNA from neonatal and adult rats.	2002 Feb	11834454
Clinical features and outcomes in children with antineutrophil cytoplasmic autoantibody-positive glomerulonephritis associated with propylthiouracil treatment.	2002 Feb	11805173
Depigmentation of brown Guinea pig skin by topical application of methimazole.	2002 Jan	11851896
Severe and mild neonatal hypothyroidism mediate opposite effects on Leydig cells of rats.	2002 Jan	11838725
Identification of active flavin-containing monooxygenase isoform 2 in human lung and characterization of expressed protein.	2002 Jan	11744609
Polarization IR spectra of model crystals containing cyclic N-H...S bonded dimers: 2-mercaptothiazoline and 2-mercapto-1-methylimidazole.	2002 Jan 15	11808728
Streptozotocin diabetes protects against arrhythmias in rat isolated hearts: role of hypothyroidism.	2002 Jan 25	11821037
Subclinical hyperthyroidism.	2002 Jan 3	11778009

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Hyperthyroidism Initial: Mild hyperthyroidism: 5 mg orally every 8 hours. Moderately severe hyperthyroidism: 10 mg orally every 8 hours (up to 40 mg per day). Severe hyperthyroidism: 20 mg orally every 8 hours. Maintenance: 5 to 15 mg orally daily.

Route of Administration: Oral

In Vitro Use Guide

Methimazole had the strongest antioxidative properties in human erythrocytes at the concentration level of 0.5 mM

Name

Type

Language

METHIMAZOLE

Common Name

English

1-Methylimidazole-2-thiol

Systematic Name

English

METHIMAZOLE [MI]

Common Name

English

METHIMAZOLE [VANDF]

Common Name

English

METHIMAZOLE [ORANGE BOOK]

Common Name

English

METHIMAZOLE [USP-RS]

Common Name

English

NSC-38608

Code

English

2H-IMIDAZOLE-2-THIONE, 1,3-DIHYDRO-1-METHYL-

Systematic Name

English

TAPAZOLE

Brand Name

English

THIAMAZOLE [MART.]

Common Name

English

THIAMAZOLE

Official Name

English

THIAMAZOLE [EP MONOGRAPH]

Common Name

English

Thiamazole [WHO-DD]

Common Name

English

thiamazole [INN]

Common Name

English

MERCAPTIZOLE

Brand Name

English

METHIMAZOLE [USP MONOGRAPH]

Common Name

English

METHIMAZOLE [HSDB]

Common Name

English

METHIMAZOLE [IARC]

Common Name

English

THIAMAZOLE [JAN]

Common Name

English

Classification Tree Code System Code

IARC

Methimazole

LIVERTOX

NBK548406