Alpha-Methyltyrosine

Alpha-methyl-p-tyrosine (AMPT) is a tyrosine hydroxylase enzyme inhibitor. Alpha-methyl-p-tyrosine (AMPT) is a non-endogenous drug involved in the catecholamine biosynthetic pathway. AMPT inhibits tyrosine hydroxylase whose enzymatic activity is regulated through the phosphorylation of different serine residue regulatory domain sites. Catecholamine biosynthesis starts with dietary tyrosine, which is hydroxylated by the enzyme tyrosine hydroxylase. It is hypothesized that AMPT competes with tyrosine at the tyrosine-binding site, causing inhibition of tyrosine hydroxylase. Alpha-methyl-p-tyrosine (AMPT) is a tyrosine hydroxylase enzyme inhibitor. Alpha-methyl-p-tyrosine (AMPT) is a non-endogenous drug involved in the catecholamine biosynthetic pathway. AMPT inhibits tyrosine hydroxylase whose enzymatic activity is regulated through the phosphorylation of different serine residue regulatory domain sites. Catecholamine biosynthesis starts with dietary tyrosine, which is hydroxylated by the enzyme tyrosine hydroxylase. It is hypothesized that AMPT competes with tyrosine at the tyrosine-binding site, causing inhibition of tyrosine hydroxylase. It has been used in the treatment of pheochromocytoma. It has been demonstrated to inhibit the production of melanin. AMPT inhibits catecholamine biosynthesis at the first step—the hydroxylation of tyrosine. Reduction in catecholamines and their metabolites (normetanephrine, metanephrine, and 4-hydroxy-3-methoxymandelic acid) result from the inhibition of tyrosine using AMPT. AMPT doses of 600 to 4,000 mg per day cause a 20 to 79 percent reduction in total catecholamines in Pheochromocytoma patients. Increase in dosage increases the magnitude of catecholamine synthesis inhibition. This increasing inhibitory effect is seen in dosages up to 1500 mg per day; at higher doses, the inhibitory effect of AMPT decreases. The maximum effect of orally administered AMPT occurs 48 to 72 hours after administration of the drug. Catecholamine production levels return to normal 72 to 96 hours after administration of the drug ceases. 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. 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. Pheochromocytoma patients exhibited a drop in blood pressure when taking AMPT. AMPT had no effect in patients with hypertension (high blood pressure). Absorption AMPT is minimally metabolized by the body and absorbed well after oral ingestion making its bioavailability high. 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. 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. Half-life The half-life of AMPT in normal patients is 3.4 to 3.7 hours. In amphetamine addicts the half-life is 7.2 hours. Elimination Small amounts of metabolites (alpha-methyldopa and alpha-methyldopamine) were found after the administration of both single-doses and maintenance-doses of AMPT. Small amounts of methyltyramine and alpha-methylnoradrenaline were found in patients undergoing AMPT therapy. Urine analysis also recovered 45 to 88 percent of unchanged AMPT after drug ingestion. Of the total AMPT excreted, 50 to 60 percent appeared in urine within the first 8 hours and 80 to 90 percent appeared within 24 hours of oral administration.