Metirosine is an antihypertensive

Antihypertensive

The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from...

 drug. It inhibits the enzyme tyrosine hydroxylase

Tyrosine hydroxylase

Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine . It does so using tetrahydrobiopterin as a coenzyme. DOPA is a precursor for dopamine, which, in turn, is a precursor for norepinephrine ...

 and, therefore, catecholamine

Catecholamine

Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...

 synthesis, which, as a consequence, depletes the levels of the catecholamines dopamine

Dopamine

Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, adrenaline and noradrenaline in the body.

Clinical use

Metirosine has been used in the treatment of pheochromocytoma

Pheochromocytoma

A pheochromocytoma or phaeochromocytoma is a neuroendocrine tumor of the medulla of the adrenal glands , or extra-adrenal chromaffin tissue that failed to involute after birth and secretes excessive amounts of catecholamines, usually noradrenaline , and adrenaline to a lesser extent...

. It is contra-indicated for the treatment of essential hypertension

Essential hypertension

Essential hypertension is the form of hypertension that by definition, has no identifiable cause. It is the most common type of hypertension, affecting 95% of hypertensive patients, it tends to be familial and is likely to be the consequence of an interaction between environmental and genetic...

.

However it is now rarely used in medicine, and its main use is in scientific research, to investigate the effects of catecholamine depletion on behaviour.

Chemistry

Metyrosine, (−)α-methyltyrosine, is synthesized in a few different ways, the simplest of which is the synthesis from 4-methoxyphenylacetone

Phenylacetone

Phenylacetone , is an organic compound. It is a clear oil with a refractive index of 1.5168. This substance is used in the manufacture of methamphetamine and amphetamine as a starting material or intermediate, where it is commonly known as P2P...

, which is reacted with potassium cyanide

Potassium cyanide

Potassium cyanide is an inorganic compound with the formula KCN. This colorless crystalline compound, similar in appearance to sugar, is highly soluble in water. Most KCN is used in gold mining, organic synthesis, and electroplating. Smaller applications include jewelry for chemical gilding and...

 in the presence of ammonium carbonate

Ammonium carbonate

Ammonium carbonate is a commercial salt with the chemical formula 2CO3. It is used when crushed as a smelling salt. It can be crushed when needed in order to revive someone who has fainted...

 to give the hydantoin

Hydantoin

Hydantoin, which is also known as glycolylurea, is a heterocyclic organic compound that can be thought of as a cyclic "double-condensation reaction" product of glycolic acid and urea...

. Treating this with hydrogen iodide

Hydrogen iodide

Hydrogen iodide is a diatomic molecule. Aqueous solutions of HI are known as iohydroic acid or hydroiodic acid, a strong acid. Gas and aqueous solution are interconvertible...

 removes the methyl-protecting group on the phenyl hydroxyl group and the product is hydrolyzed by barium hydroxide

Barium hydroxide

Barium hydroxide is the chemical compound with the formula Ba2. Also known as baryta, it is one of the principal compounds of barium. The white granular monohydrate is the usual commercial form.-Preparation:...

 into a racemic

Racemic

In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

mixture of α-methyl-D,L-tyrosine, from which the desired L-isomer is isolated.

• K. Potts, J. Chem. Soc., 1632 (1955).
• G.A. Stein, I.K. Pfister, (1959).