L-tyrosine potentiates the anorexia induced by mixed-acting sympathomimetic drugs in hyperphagic rats.
The effects of L-tyrosine (L-TYR) on the anorectic activity of several mixed-acting sympathomimetics were determined during the dark cycle in rats made hyperphagic by food deprivation. L-TYR (200 mg/kg) significantly potentiated the anorectic activity of phenylpropanolamine, (-)-ephedrine and (+)-amphetamine by 48, 50 and 37%, respectively. When the dose of L-TYR was varied (25-400 mg/kg), a significant dose-dependent relationship was noted. The observed potentiation was positively correlated with increases in brain TYR concentrations; blockade of L-TYR uptake into the brain by the coadministration of L-valine prevented this potentiation. Various other L-amino acids, as well as D-TYR, failed to mimic the potentiating action of L-TYR. As determined by alpha-methyl-p-TYR pretreatment, the L-TYR-induced potentiation was dependent upon increased catecholamine synthesis. Although various other mixed-acting sympathomimetic anorexiants were similarly potentiated by L-TYR, the direct-acting beta-2 adrenoceptor anorexiants, salbutamol and methoxyphenamine, were not. These results indicate that L-TYR specifically potentiates the anorectic activity of the studied mixed-acting sympathomimetics and are consistent with the requirement of the central conversion of L-TYR to catecholamines via TYR hydroxylase for this response. The possibility that the effect of mixed-acting sympathomimetics is normally limited by the availability of L-TYR is suggested.
Hull
K M
KM
Department of Pharmacology, Massachusetts College of Pharmacy and Allied Health Sciences, Boston.
Maher
T J
TJ
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects; D006963:Hyperphagia / Q000503:physiopathology; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D010649:Phenylalanine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013566:Sympathomimetics / Q000494:pharmacology*; D014443:Tyrosine / Q000032:analysis / Q000494:pharmacology*; D014633:Valine / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D000596:Amino Acids; D008781:Methyltyrosines; D013566:Sympathomimetics; D014443:Tyrosine; D010649:Phenylalanine; D019805:alpha-Methyltyrosine; D014633:Valine