RT Journal Article
SR Electronic
T1 TOXICOLOGIC STUDIES WITH α-METHYLTYROSINE, AN INHIBITOR OF TYROSINE HYDROXYLASE
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 506
OP 515
VO 155
IS 3
A1 K. E. Moore
A1 P. F. Wright
A1 J. K. Bert
YR 1967
UL http://jpet.aspetjournals.org/content/155/3/506.abstract
AB α-Methyltyrosine (αMT) has been used to deplete tissues of their catecholamine stores. After the intraperitoneal injection of 200 mg/kg of αMT, 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 αMT 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 αMT. The delayed death may result from renal damage per se or from the prolonged high concentration of αMT 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), αMT depleted tissues of their catecholamine stores without producing concomitant renal damage and its sequelae. © 1967 by The Williams & Wilkins Company