Effect of tyrosine on the potentiation by aspartame and phenylalanine of metrazol-induced convulsions in rats.
Male rats were treated by oral intubation with tyrosine (Tyr), at doses of 0.5 and 1.0 g/kg body weight, alone or together with 1 g aspartame (APM)/kg body weight, or an equivalent dose of phenylalanine (Phe; 0.5 g/kg body weight); the effects on seizures induced by an effective dose of metrazol (ED50) were observed. Tyr (0.5 g/kg body weight) had a protective effect against the Phe-potentiation of metrazol-induced clonic-tonic convulsions. At the same dose Tyr had no effect on the seizure-promoting activity of APM, but at 1 g/kg it reduced the proconvulsant potential of the sweetener. Analysis of the brain and plasma amino acid concentrations indicated that the Tyr to Phe ratio tended to be enhanced in Tyr-Phe treated rats compared with those treated with Phe alone. This ratio remained essentially constant in the brain of APM-treated rats, compared with those treated with APM plus 1 g Tyr/kg body weight, whereas an increase in this ratio in the plasma was observed. These results confirm that Tyr antagonizes the proconvulsant effect of Phe and APM and they further suggest that no simple relationship exists between the relative brain concentrations of the two amino acids and the response to metrazol convulsions.
Guiso
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Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea, Milan, Italy.
Diomede
L
L
Romano
M
M
Caccia
S
S
Sarati
S
S
Salmona
M
M
D000818:Animals; D001218:Aspartame / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D008297:Male; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010649:Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced*; D014443:Tyrosine / Q000378:metabolism / Q000494:pharmacology*
D014443:Tyrosine; D010649:Phenylalanine; D010433:Pentylenetetrazole; D001218:Aspartame