THE WEIGHT-DEPRESSING ACTION OF α-METHYL-DL-TRYPTOPHAN IN THE RAT

Abstract

α-Methyl-DL-tryptophan, injected intraperitoneally into rats, has a weight-depressing action lasting up to 72 hours. Dosages in the range 0.015–2.0 millimoles/kg body weight (3.3–436 mg/kg) are effective. Attempts to antagonize the weight-depressing action by giving essential amino acids and B vitamins were unsuccessful. Metabolic studies have shown that about half the injected dose of the compound (or its derivatives), as measured by the Hopkins–Cole glyoxylic acid reaction, is excreted in the urine in 24 hours; most of this appears during the first 4 hours after the injection. Ina search for an explanation for the weight-depressing action of α-methyltryptophan, tryptophan pyrrolase activity in the liver was estimated. This enzymic activity increases for 8 hours after the injection of α-methyltryptophan, and thereafter remains high for 72 hours. Tryptophan-injected animals showed increases in tryptophan pyrrolase level for 1.5 hours, and a return to normal concentrations within 24 hours. Other α-methyl amino acids which were tested had no comparable effect on body weight.