TOXICOLOGIC STUDIES WITH -METHYLTYROSINE, AN INHIBITOR OF TYROSINE HYDROXYLASE

¹ Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire

-Methyltyrosine (MT) has been used to deplete tissues of their catecholamine stores. After the intraperitoneal injection of 200 mg/kg of MT, 40% of the rats became depressed, lethargic, hypothermic and emaciated. These effects were marked by the 20th hr, and the animals died 28 to 48 hr after injection. Approximately 80% of rats receiving 300 mg/kg of MT were similarly affected. Rats exhibiting overt signs of toxicity had high blood urea nitrogen levels and excreted large volumes of urine with abnormally high contents of glucose and protein. These results, along with histologic evidence, were indicative of kidney damage. One consequence of this injury was the inability of the affected animals to excrete MT. The delayed death may result from renal damage per se or from the prolonged high concentration of MT in the tissues. The renal injury was prevented by repeated oral administration of water. When administered by the oral route (200 mg/kg) or by multiple intraperitoneal injections of small doses (50 mg/kg every 4 hr), MT depleted tissues of their catecholamine stores without producing concomitant renal damage and its sequelae.

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