Tiratricol

Warning

H302 (97.6%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P270, P271, P280, P301+P317, P302+P352, P304+P340, P317, P321, P330, P362+P364, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 42 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Orally, tiratricol can cause severe diarrhea, fatigue, lethargy, and profound weight loss. Heart attacks and strokes are possible, as well as symptoms of hyperthyroidism, including increased appetite, abdominal cramps, tremors, menstrual irregularities, nervousness, insomnia, sweating, intolerance to heat, fever, palpitations, tachycardia, increased pulse and blood pressure, chest pain, and cardiac arrhythmias. Case reports have implicated tiratricol in centrally-mediated hypothyroidism, pseudohypothyroidism, internuclear ophthalmoplegia, and hepatotoxicity. (L2139) It has been investigated for use in reducing goiter. It has also shown some effectiveness in reducing the atrophy caused when using corticosteroids. (Wikipedia) Tiratricol has been used to suppress pituitary TSH secretion, with reported attenuation of extrapituitary thyromimetic effects. (A15459)

Tiratricol is a naturally occurring metabolite of T4 (thyroxine) and a structural analog of T3 (triiodothyronine). Low concentrations of tiratricol are found in plasma, but tiratricol has no known role in thyroid physiology. Tiratricol has a high affinity for T3 receptors and suppresses thyroid stimulating hormone (TSH) secretion at therapeutic doses without causing significant peripheral effects, such as increased basal metabolism rate and heart rate. Tiratricol might lower total and LDL cholesterol, and stimulate bone formation. About 67% of an oral dose of tiratricol is absorbed; the half-life is 6 hours. (L2139) Serum sex hormone-binding globulin levels increased 55 +/- 13% with tiratricol, indicating an augmented hepatic response to tiratricol. Tiratricol had effected the cardiovascular function. Tiratricol has distinct augmented hepatic and skeletal thyromimetic actions of potential therapeutic value. (A15458)

D - Dermatologicals

H - Systemic hormonal preparations, excl. sex hormones and insulins

QH - Systemic hormonal preparations, excl. sex hormones and insulin

QD - Dermatologicals

Tiratricol exerts thyromimetic effects and inhibits TSH secretion in humans to lower endogenous thyroid hormone production. Studies suggest enhanced hepatic and skeletal thyromimetic actions by tiratricol. Symptoms of hyperthyroidism have been documented in case reports with the use of dietary supplement tiratricol. Tiratricol was reported to mediate some antiviral and antibacterial activities, though these effects warrant further investigations.

Monocarboxylate transporter 8 (MCT8) is involved in the transport of triiodothyronine (T3) and thyroxine (T4). Mutations in the SLC16A2 gene leading to MCT8 deficiency lead to impaired thyroid hormone uptake into the brain and elevated serum concentrations of T3. Tiratricol is biologically active, binds with high affinity to the thyroid hormone receptors TRα and TRβ and exerts similar biological effects to T3, although with different tissue specificity. Unlike T3 and T4, tiratricol enters MCT8 dependent cells without a functioning MCT8 transporter. Tiratricol can thereby replace T3 in MCT8 dependent tissues and restore normal thyroid hormone activity across tissues.

After reaching the maximum plasma concentrations, the serum concentrations of tiratricol declined in a generally biphasic manner and remained quantifiable until between three and 48 hours post dose. The geometric mean half-life ranged from 13.3 to 14.0 hours for the 350 microgram and 1050 microgram doses, respectively.

Tiratricol is a naturally circulating metabolite of active T3 with a high degree of structural similarity and follows the same metabolic pathway. The major human metabolic pathway of tiratricol is by stepwise deiodination, sulfation and glucuronidation mainly in the liver, similar to T3. Specific metabolic reactions and metabolites of tiratricol have not been characterized.