Interspecies and interstrain studies on the increased susceptibility to metrazol-induced convulsions in animals given aspartame.
The ability of aspartame (APM) to increase the susceptibility to metrazol-induced convulsions was studied in two strains of mice (CD1 and DBA/2J) and in guinea-pigs. Rats were included as known positive controls. Plasma and brain levels of phenylalanine (Phe) and tyrosine (Tyr) were measured in CD1 mice and guinea-pigs at various intervals after a dose of 1 g APM/kg body weight (administered orally to mice and ip to guinea-pigs). In mice, peak levels of Phe and Tyr were observed in plasma after 30 min and in brain after 60 min. In guinea-pigs peak plasma levels of Phe and Tyr occurred 30 min after treatment. Phe was at a maximum in guinea-pig brain after 30 min, while Tyr levels reached a peak at 120 min. In further experiments Phe and Tyr levels were measured 1 hr after APM doses of 0.5, 0.75 or 1 g/kg. In CD1 mice, plasma Phe and Tyr levels were increased significantly only at the highest dose, whereas in brain, Tyr concentrations were significantly increased by 0.75 or 1 g APM/kg and Phe was significantly increased by all three doses. In the guinea-pig, plasma Phe and Tyr were increased significantly only by 1 g APM/kg and in brain this dose significantly raised only the Phe levels. Monoamine and metabolite levels were determined in the brain striata of CD1 and DBA/2J mice 1 hr after the oral administration of 1 or 2 g APM/kg body weight; no differences from control values were found in either strain. The studies of potentiation of metrazol-induced convulsions showed that APM, at doses of up to 2 g/kg body weight, had no such effect in mice or guinea-pigs. In contrast, as expected, the potentiation was significant in the rat at 1 g/kg.
Diomede
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Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Romano
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Guiso
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Caccia
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Nava
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Salmona
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D000818:Animals; D001218:Aspartame / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010433:Pentylenetetrazole; D010649:Phenylalanine / Q000097:blood / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism; D013045:Species Specificity; D014443:Tyrosine / Q000097:blood / Q000378:metabolism
D014443:Tyrosine; D010649:Phenylalanine; D010433:Pentylenetetrazole; D001218:Aspartame