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

Molecular Formula	C4H6N2S
Molecular Weight	114.169
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 8146

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyperthyroidism 13 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040320s005lbl.pdf	Primary		Approved 8307	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 1532	inhibitor 1695	inhibitor 1789

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCTN1 29 CYP2E1 846 CYP1A2 1463 CYP2C19 1410 CYP2A6 670 CYP2B6 770

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1857	inhibitor 3185 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	major [IC50 14 uM]
CYP2A6 702	inhibitor 3185 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	no [IC50 >/=1000 uM]
CYP2C19 1484	inhibitor 3185 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	no [IC50 >/=1000 uM]
CYP2D6 1826	inhibitor 3185 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	no [IC50 >/=1000 uM]
CYP2E1 929	inhibitor 3185 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	no [IC50 >/=1000 uM]
CYP2B6 946	inhibitor 3185 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	weak [IC50 100 uM]
CYP2C9 1747	inhibitor 3185 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	weak [IC50 100 uM]
CYP1A2 1620	inhibitor 3185 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060560	weak [Inhibition 50 uM]
OCTN1 29	inhibitor 3185 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
Sequencing, expression, and characterization of cDNA expressed flavin-containing monooxygenase 2 from mouse.	2001	11835629
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
Role of thyroid hormones in the maturation and organisation of rat barrel cortex.	2001	11718994
[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
[Graves-Basedow disease associated with unusual variation of thyroid papillary carcinoma: a clinical case].	2001 Apr-Jun	11688359
Estimation of antithyroid drug dose in Graves' disease: value of quantification of thyroid blood flow with color duplex sonography.	2001 Aug	11527601
[Long-term results of ultrasound-guided ethanol injections in patients with autonomous thyroid nodules and hyperthyroidism].	2001 Aug 15	11560045
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
Hypothyroidism induces type I iodothyronine deiodinase expression in tilapia liver.	2001 Dec	11742517
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
A case of thyrotoxicosis with pancytopenia.	2001 Jun	11523911
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
Methimazole-induced pulmonary hemorrhage associated with antimyeloperoxidase-antineutrophil cytoplasmic antibody: a case report.	2001 Nov	11802538
Hyperemesis gravidarum associated with thyrotoxicosis and a past history of an eating disorder.	2001 Nov	11789755
Influence of nicotinamide on the radiosensitivity of normal and goitrous thyroid in the rat.	2001 Nov	11762708
Adverse effects of prenatal methimazole exposure.	2001 Nov	11745832
Effect of eicosapentaenoic acid ethyl ester on hypothyroid function.	2001 Nov	11691645
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
Effects of neonatal hypothyroidism on the expressions of growth cone proteins and axon guidance molecules related genes in the hippocampus.	2001 Nov 26	11694350
Severe myocardial ischemia following hormone replacement in two cases of hypothyroidism with normal coronary arteriogram.	2001 Oct	11789561
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
Selective effect of hypothyroidism on expression of myelin markers during development.	2001 Oct 15	11592121
Thyroid hormones modify susceptibility to lidocaine-kindling in rats.	2001 Oct 19	11712661
Antithyroid drugs as a factor influencing the outcome of radioiodine therapy in Graves' disease and toxic nodular goitre?	2001 Sep	11585295
Effect of losartan on sodium appetite of hypothyroid rats subjected to water and sodium depletion and water, sodium and food deprivation.	2001 Sep	11571491
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
The effect of methimazole on thyroid uptake of pertechnetate and radioiodine in normal cats.	2001 Sep-Oct	11678569
Neonatal hyperthyroidism in infants of mothers previously thyroidectomized due to Graves' disease.	2001 Sep-Oct	11592578
Dermatomyositis and Graves' disease.	2001 Sep-Oct	11579725
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
Teratogen update: antithyroid drugs-methimazole, carbimazole, and propylthiouracil.	2002 Jan	11835230
Methimazole-induced asthma?	2002 Jan	11796476
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

Substance Class	Chemical Created by `admin` on `Fri Dec 16 16:03:04 UTC 2022` Edited by `admin` on `Fri Dec 16 16:03:04 UTC 2022`
Record UNII	554Z48XN5E
Record Status	`Validated (UNII)`
Record Version

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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