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.[10]
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.[11] Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) may increase recovery.
Other known side effects include:
skin rash
itching
abnormal hair loss
upset stomach
vomiting
loss of taste
abnormal sensations (tingling, prickling, burning, tightness, and pulling)
Have ever had any blood disease, such as decreased white blood cells (leukopenia), decreased platelets (thrombocytopenia) or aplastic anemia, or liver disease (hepatitis, jaundice)[16]
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).[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.
A study has shown that it modulates secretion of CXCL10.[17]
The cyclic thiourea derivative thiamazole is a white to matte brown crystalline powder with a characteristic odour. The boiling point is 280 °C (decomposition). Thiamazole is soluble in water, ethanol and chloroform, but hardly soluble in ether.[19]
Thiamazole has been known since 1889,[22] when it was made by a two-stage process starting from 2,2-diethoxyethaneamine, which was reacted with methyl isothiocyanate.[23]
The product of this reaction was then cyclised in an acid-catalysed reaction to form thiamazole.[23]
When the therapeutic potential of thiamazole was recognised in the late 1940s, a number of alternative routes were developed based, for example, on the use of 2-chloro-1,2-diethoxyethane as starting material, in a reaction with methylamine.
The resulting intermediate can be treated with potassium thiocyanate in the presence of acid to give thiamazole.[23]
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.[10][24] In 1949 he published his work on thiamazole which showed its superiority to previous therapies.[10] The compound had been known since 1889,[22][23] and was developed as a drug by Eli Lilly and Company under the trade name Tapazole.[25]
^World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
^ abcBurch HB, Cooper DS (October 2018). "ANNIVERSARY REVIEW: Antithyroid drug therapy: 70 years later". European Journal of Endocrinology. 179 (5): R261–R274. doi:10.1530/EJE-18-0678. PMID30320502.
^Fumarola A, Di Fiore A, Dainelli M, Grani G, Calvanese A (November 2010). "Medical treatment of hyperthyroidism: state of the art". Experimental and Clinical Endocrinology & Diabetes. 118 (10): 678–684. doi:10.1055/s-0030-1253420. PMID20496313.
^Pharmacovigilance Risk Assessment Committee (PRAC) (4 January 2019). "PRAC recommendations on signals"(PDF). European Medicines Agency. EMA/PRAC/826440/2018.
^Busenbark LA, Cushnie SA (June 2006). "Effect of Graves' disease and methimazole on warfarin anticoagulation". The Annals of Pharmacotherapy. 40 (6): 1200–1203. doi:10.1345/aph.1G422. PMID16735660.
^Caney S (2012). "Managing hyperthyroidism in cats". Veterinary Times. 42 (46): 12–15.
^Entry on Thiamazol. at: Römpp Online. Georg Thieme Verlag, retrieved 10. November 2014.
^Taylor JJ, Willson RL, Kendall-Taylor P (29 October 1984). "Evidence for direct interactions between methimazole and free radicals". FEBS Letters. 176 (2): 337–340. doi:10.1016/0014-5793(84)81192-8. S2CID86322153.
^ abcdBaranov VV, Galochkin AA, Kravchenko AN (August 2023). "A novel approach to the synthesis of methimazole". Russian Chemical Bulletin. 72 (8): 1946–1949. doi:10.1007/s11172-023-3983-y.
^Astwood EB (1984). "Landmark article May 8, 1943: Treatment of hyperthyroidism with thiourea and thiouracil. By E.B. Astwood". JAMA: The Journal of the American Medical Association. 251 (13): 1743–1746. doi:10.1001/jama.251.13.1743. PMID6422063.
