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.]
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.][ 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 .][
]
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 also available in Europe and Asia.]
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.
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.
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)
-
swelling
-
arthralgia and myalgia
-
drowsiness
-
dizziness
-
decreased platelet count (thrombocytopenia)
-
aplasia cutis congenita (prenatal exposure)
-
goiter (prenatal exposure)
-
choanal atresia (prenatal exposure during the first trimester of pregnancy)
-
acute pancreatitis
Interaction
Adverse effects may occur for individuals who:
-
Take ('blood thinners') such as warfarin (Coumadin),
-
Have ever had any blood disease, such as decreased white blood cells (leukopenia), decreased platelets (thrombocytopenia) or aplastic anemia, or liver disease (hepatitis, jaundice)
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).
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.
Chemical properties
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.
Thiamazole acts as a free radical scavenger for radicals such as the hydroxyl radical (•OH) radical.
Laboratory synthesis
Thiamazole has been known since 1889,
The product of this reaction was then cyclised in an acid-catalysed reaction to form thiamazole.[
]
Manufacture
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.[
]
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.[ The compound had been known since 1889,][ and was developed as a drug by Eli Lilly and Company under the trade name Tapazole.]
Veterinary uses
Thiamazole is commonly used in cats to treat hyperthyroidism.
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.
Hepatotoxicity also occurs in a small but notable amount of cats treated with thiamazole.
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.[ ][
]
/ref> Felanorm contains the same active ingredient (methimazole) as the approved brand name drug product, Felimazole Coated Tablets, which were first approved in May 2009.
