α-Methyl-p-tyrosine (AMPT), or simply α-methyltyrosine, also known in its chiral 2-(S) form as metirosine, is a tyrosine hydroxylase enzyme inhibitor and is therefore a drug involved in inhibiting the catecholamine biosynthetic pathway.

[1] AMPT inhibits tyrosine hydroxylase whose enzymatic activity is normally regulated through the phosphorylation of different serine residues in regulatory domain sites.

[9] AMPT doses of 600 to 4,000 mg per day cause a 20 to 79 percent reduction in total catecholamines in Pheochromocytoma patients.

[11] Dosages as low as 300 mg per day have been found to have an effect on catecholamine production, which can be measured through urinary excretion analysis and cerebral spinal fluid assays.

[9] AMPT is successful at inhibiting catecholamine production in humans whether the rate of synthesis is high, as in pheochromocytoma, or normal as in patients with hypertension.

[9] Single-dose studies have shown that a 1,000 mg dose results in AMPT levels in the plasma of 12-14 μg/mL after 1 to 3 hours of ingestion.

[11] Maintenance-dose studies have shown that absorption of AMPT is overall the same in all individuals taking doses in the range of 300-4,000 mg per day.

Pheochromocytoma is a rare neuroendocrine tumor that results in the release of too much epinephrine and norepinephrine, hormones that control heart rate, metabolism, and blood pressure.

[14] AMPT was used in the 1960s for preoperative pharmacological control of catecholamine overexpression that causes hypertension and other arterial and cardiac abnormalities.

[1] Therapy with AMPT could prove to be more specific to dopamine and therefore eliminate some of the negative side effects of antipsychotic drugs.

[17] Cocaine administration abruptly and reversibly increases both the Vmax of dopamine uptake and the Bmax of vesicular monoamine transporter 2 (VMAT-2) ligand (dihydrotetrabenazine) binding.

Although it is not well understood, this relationship allows for AMPT’s inhibitory property, which blocks tyrosine hydroxylase, to increase dopamine transport by the vesicle monoamine transporter-2.

[18] Additionally, administration of reserpine when dopamine is maximally depleted causes neurotoxic effects, which does not occur with AMPT treatment.

[20] There is evidence that catecholamine depletion causes an increase in sleepiness that is more pronounced than sleep deprivation, and that the fatigue lingers after the drug is discontinued.

[22] Patients have reported hand, leg, and trunk tremors as well as tightening of the jaw post AMPT drug therapy.