THYROXINE

THYROXINE

Thyroxine is a tetraiodoamino acid of the thyroid gland and exerts à stimulatingeffecton metabolism. Its naturaloccurrence in the free state has not been reported. It may be a cleavage product of thyroglobulin. The L-form is twice as active physiologically as the racemic product; the D-form has very less activity.

For the synthesis of thyroxine, L-tyrosine is nitrated, the nitro-derivative is acetylated at the amino group, followed by esterification. For the synthesis of 4-methoxyphenyl ether, toluene-4-sulphonyl ester is prepared using tosyl chloride and the ester reacts with 4-methoxyphenol in pyridine to form the desired ether. The nitro groups are reduced, the di-amino tetrazotized, and the tetrazonium salt reacted with iodine in sodium iodide solution to yield the diiodo derivative. Chemical reduction with a mixture of hydriodic acid, red phosphorus and glacial acetic acid produces L-3,5-diiodothyronine, which on iodination in ethylamine gives L-thyroxine.

DL-Thyroxine, needle-like crystals. m.p. 231-233 (decomp), is insoluble in alcohol and other organic solvents. In the presence of mineral acids or alkalies it dissolves in alcohol; soluble in solutions of the alkali hydroxides and in hot solutions of the alkali carbonates.

L-Thyroxine, m.p. 235-2369 (decomp), is used in the form of sodium salt, known as sodium Levothyroxine.

Sodium Levothyroxine (Brand Names : L-Thyroxin sodium salt; Levothyroxine sodium; Elitroxin; Euthyrox; LaevOxin; Letter; Levaxin; Levothroid; Oroxine; Synthroid sodium; Thyroxevan). It is the sodium salt of the laevo isomer of thyroxine or prepared synthetically. It occurs as an odourless, white to pale brownishyellow, tasteless, hygroscopic, amorphous or crystalline powder. It may assume a slight pink colour on exposure to light. It is very slightly soluble in water and chloroform; slightly soluble in alcohol; practically insoluble in acetone, chloroform and ether; soluble in solutions of alkali hydroxides and in hot solutions of alkali carbonates. A saturated solution in water has a pH of about 8.9.

Uses : Thyroxire is used in the treatment of thyroid-deficien conditions and to treat hypothyroidism occurring in patients after therapy for thyroid cancer.

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Adverse Effect

The adverse effects of thyroid hormones are generally associated with excessive dosage. The effects may include tachycardia, palpitations, anginal pain, cardiac arrhythmias. headache, nervousness, excitability, restlessness, insomnia, cramps in skeletal muscle, muscular weakness, tremors, sweating. flushing, fever, diarrhoea, vomiting and loss of weight.