Thiamazole

Overview

Thiamazole, also known as methimazole, is a medication used to treat hyperthyroidism. This includes Graves' disease, toxic multinodular goiter, and thyrotoxic crisis. It is taken by mouth. Full effects may take a few weeks to occur.[1][2] WP

Common side effects include itchiness, hair loss, nausea, muscle pain, swelling, and abdominal pain. Severe side effects may include low blood cell counts, liver failure, and vasculitis. Use is not recommended during the first trimester of pregnancy due to the risk of congenital anomalies, but it may be used in the second trimester or third trimester. It may be used during breastfeeding. Those who developed significant side effects may also have problems with propylthiouracil. Thiamazole is a cyclic thiourea derivative that works by decreasing the production of thyroid hormones.[1][3] WP

Thiamazole was approved for medical use in the United States in 1950. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. It is also available in Europe and Asia. In 2023, it was the 255th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[1][4–8] WP

Uses, dosage and effects

Medical uses

Thiamazole is a drug used to treat hyperthyroidism such as in Graves' disease, a condition that occurs when the thyroid gland begins to produce an excess of thyroid hormone. The drug may also be taken before thyroid surgery to lower thyroid hormone levels and minimize the effects of thyroid manipulation. Additionally, thiamazole is used in the veterinary setting to treat hyperthyroidism in cats.[9] WP

Veterinary uses

Thiamazole is commonly used in cats to treat hyperthyroidism.[10] WP

Despite 20% of cats treated with thiamazole testing positive for antinuclear antibody lupus erythematosus and immune-mediated haemolytic anemia, neither condition is associated with thiamazole in cats.[10] WP

Hepatic toxicity also occurs in a small but notable amount of cats treated with thiamazole.[10] WP

In July 2024, the US Food and Drug Administration (FDA) approved Felanorm, the first generic methimazole oral solution for the treatment of hyperthyroidism in cats. Felanorm contains the same active ingredient (methimazole) as the approved brand name drug product, Felimazole Coated Tablets, which were first approved in May 2009. In addition, the FDA determined that Felanorm contains no inactive ingredients that may significantly affect the bioavailability of the active ingredient. Felanorm is sponsored by Norbrook Laboratories based in the United Kingdom.[11][12][13] WP

Risks and side effects

Adverse effects

It is important to monitor any symptoms of fever or sore throat while taking thiamazole; this could indicate the development of agranulocytosis, an uncommon but severe side effect resulting from a drop in the white blood cell count (to be specific, neutropenia, a deficiency of neutrophils). A complete blood count (CBC) with differential is performed to confirm the suspicion, in which case the drug is discontinued. Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) may increase recovery.[14] WP

Liver injury

Methimazole is commonly associated with transient, mild, asymptomatic elevations in serum aminotransferase levels, typically during the first months of treatment with a high dose. More serious liver injury can, usually with a cholestatic or mixed pattern of enzyme elevations and prolonged cholestatic hepatitis. Methimazole induced liver injury fatalities are rare and symptoms and jaundice usually clear within 2-8 weeks of stopping the drug. In most cases switching to propylthiouracil does not result in a recurrence of liver injury.[15][16] WP

To differentiate methimazole induced liver injury from liver injury related to the underlying hyperthyroidism, it is recommended to check baseline liver enzymes prior to initiation of treatment.[17] WP

Other known side effects include: WP

• skin rash WP
• itching WP
• abnormal hair loss WP
• upset stomach WP
• vomiting WP
• loss of taste WP
• abnormal sensations (tingling, prickling, burning, tightness, and pulling) WP
• swelling WP
• joint and muscle pain WP
• drowsiness WP
• dizziness WP
• decreased platelet count (thrombocytopenia) WP
• aplasia cutis congenita (prenatal exposure) WP
• thyroid gland enlargement (prenatal exposure) WP
• choanal atresia (prenatal exposure during the first trimester of pregnancy) WP
• acute pancreatitis[18][19][20] WP

Pharmacology

Mechanism of action

Thiamazole inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis by oxidizing the anion iodide (I⁻) to iodine (I₂), hypoiodous acid (HOI), and enzyme linked hypoiodate (EOI), facilitating iodine's addition to tyrosine residues on the hormone precursor thyroglobulin, a necessary step in the synthesis of triiodothyronine (T₃) and thyroxine (T₄). WP⚠ Wikipedia itself has flagged this text: citation needed.

It does not inhibit the action of the sodium-dependent iodide transporter located on follicular cells' basolateral membranes. Inhibition of this step requires competitive inhibitors such as perchlorate and thiocyanate. WP

A study has shown that it modulates secretion of CXCL10.[21] WP

History

History

Surgery was used to treat hyperthyroidism until the advent of drug therapies in the 1940s. In 1942, thiourea was used by Edwin B. Astwood to treat a patient with the condition. He later published evidence that thiouracil was more effective and began a search for analogues with higher potency and less toxicity. In 1949 he published his work on thiamazole which showed its superiority to previous therapies. The compound had been known since 1889, and was developed as a drug by Eli Lilly and Company under the trade name Tapazole.[9][22–25] WP

Chemistry

Formula

C4H6N2S PC

CAS number

60-56-0 PC

Molar mass (g/mol)

114.17 PC

IUPAC name (computed by PubChem)

3-methyl-1H-imidazole-2-thione PC

SMILES

CN1C=CNC1=S PC

InChIKey

PMRYVIKBURPHAH-UHFFFAOYSA-N PC

PubChem CID

1349907

IUPAC name

1-Methyl-3H-imidazole-2-thione WP

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Methimazole Monograph for Professionals
2. Other Spina D. The Flesh and Bones of Medical Pharmacology E-Book. 2008
3. Other Methimazole Use During Pregnancy
4. Other World Health Organization model list of essential medicines: 21st list 2019. 2019
5. Other World Health Organization model list of essential medicines: 22nd list (2021). 2021
6. Journal / agency Yoshihara A, Noh J, Yamaguchi T, Ohye H, Sato S, Sekiya K, Kosuga Y, Suzuki M, Matsumoto M, Kunii Y, Watanabe N, Mukasa K, Ito K, Ito K. Treatment of graves' disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation. The Journal of Clinical Endocrinology and Metabolism. July 2012. doi:10.1186/1756-6614-8-S1-A12 · PMID 22547422 · PMC4480840
7. Other Kane SP. The Top 300 of 2023
8. Other Kane SP. Methimazole Drug Usage Statistics, United States, 2014 - 2023
9. Journal / agency Burch HB, Cooper DS. ANNIVERSARY REVIEW: Antithyroid drug therapy: 70 years later. European Journal of Endocrinology. October 2018. doi:10.1530/EJE-18-0678 · PMID 30320502
10. Journal / agency Canine and feline endocrinology. 2015
11. Journal / agency Center for Veterinary Medicine. FDA Approves First Generic Methimazole for Treating Hyperthyroidism in Cats. 9 July 2024
12. Journal / agency Center for Veterinary Medicine. Recent Animal Drug Approvals. 2 December 2024
13. Journal / agency fda.gov
14. Journal / agency Fumarola A, Di Fiore A, Dainelli M, Grani G, Calvanese A. Medical treatment of hyperthyroidism: state of the art. Experimental and Clinical Endocrinology & Diabetes. November 2010. doi:10.1055/s-0030-1253420 · PMID 20496313
15. Journal / agency LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31643725
16. Journal / agency Pollack R, Stokar J. Risk of Significant Liver Enzyme Elevation After Switching Antithyroid Drugs. European Journal of Endocrinology. July 2026. doi:10.1093/ejendo/lvag123 · PMID 42478868
17. Journal / agency Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, Walter MA. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid®. October 2016. doi:10.1089/thy.2016.0229 · PMID 27521067
18. Journal / agency Pecere A, Caputo M, Sarro A, Ucciero A, Zibetti A, Aimaretti G, Marzullo P, Barone-Adesi F. Methimazole Treatment and Risk of Acute Pancreatitis: A Population-based Cohort Study. The Journal of Clinical Endocrinology and Metabolism. December 2020. doi:10.1210/clinem/dgaa544 · PMID 32813014
19. Journal / agency Brix TH, Lund LC, Henriksen DP, Folkestad L, Bonnema SJ, Hallas J, Hegedüs L. Methimazole and risk of acute pancreatitis. The Lancet. Diabetes & Endocrinology. March 2020. doi:10.1016/s2213-8587(20)30025-5 · PMID 32035032
20. Journal / agency Pharmacovigilance Risk Assessment Committee (PRAC). PRAC recommendations on signals. 4 January 2019
21. Journal / agency Crescioli C, Cosmi L, Borgogni E, Santarlasci V, Gelmini S, Sottili M, Sarchielli E, Mazzinghi B, Francalanci M, Pezzatini A, Perigli G, Vannelli GB, Annunziato F, Serio M. Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes. The Journal of Endocrinology. October 2007. doi:10.1677/JOE-07-0240 · PMID 17911406
22. Journal / agency Astwood EB. Landmark article May 8, 1943: Treatment of hyperthyroidism with thiourea and thiouracil. By E.B. Astwood. JAMA: The Journal of the American Medical Association. April 1984. doi:10.1001/jama.251.13.1743 · PMID 6422063
23. Journal / agency Wohl A, Marckwald W. Ueber Condensations-producte aus Amidoacetal. (II.). Berichte der Deutschen Chemischen Gesellschaft. 1889. doi:10.1002/cber.188902201280
24. Journal / agency Baranov VV, Galochkin AA, Kravchenko AN. A novel approach to the synthesis of methimazole. Russian Chemical Bulletin. August 2023. doi:10.1007/s11172-023-3983-y
25. Journal / agency Davidson LA. Clinical trial of methimazole in treatment of thyrotoxicosis. British Medical Journal. December 1953. doi:10.1136/bmj.2.4849.1300 · PMID 13106417 · PMC2030295

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