Dailey J W, Lasley S M, Mishra P K, Bettendorf A F, Burger R L, Jobe P C
Department of Basic Sciences, University of Illinois College of Medicine, Peoria 61656.
Toxicol Appl Pharmacol. 1989 May;98(3):475-86. doi: 10.1016/0041-008x(89)90176-2.
Concentrations of plasma amino acids and brain monoamines as well as pentylenetetrazol-induced seizures were monitored in CD-1 mice treated with aspartame in acute oral doses from 0 to 2500 mg/kg. One hour after administration aspartame produced increases in plasma concentrations of phenylalanine and tyrosine and modest reductions in concentrations of brain serotonin and 5-hydroxyindole acetic acid. However, these effects of the sweetener had no influence on the convulsive dose fifty (CD50) of pentylenetetrazol. Moreover, aspartame failed to alter the percentage of mice exhibiting seizures when exposed to an approximate CD50 of pentylenetetrazol. Finally, aspartame had no effect on brain norepinephrine or dopamine concentrations. In sharp contrast to previously reported studies, these observations suggest that aspartame, given in heroic doses, does not alter the propensity to seizure activity in CD-1 mice. We conclude that changes in plasma amino acids and brain serotonin produced by large oral bolus doses of aspartame are insufficient to result in functional deficits which might have the capacity to facilitate pentylenetetrazol-induced seizures.
在以0至2500毫克/千克的急性口服剂量给予阿斯巴甜处理的CD - 1小鼠中，监测血浆氨基酸、脑单胺的浓度以及戊四氮诱发的癫痫发作情况。给药一小时后，阿斯巴甜使血浆苯丙氨酸和酪氨酸浓度升高，并使脑血清素和5 - 羟吲哚乙酸浓度适度降低。然而，这种甜味剂的这些作用对戊四氮的惊厥剂量五十（CD50）没有影响。此外，当暴露于近似戊四氮CD50时，阿斯巴甜未能改变出现癫痫发作的小鼠百分比。最后，阿斯巴甜对脑去甲肾上腺素或多巴胺浓度没有影响。与先前报道的研究形成鲜明对比的是，这些观察结果表明，给予大剂量的阿斯巴甜不会改变CD - 1小鼠癫痫发作活动的倾向。我们得出结论，大剂量口服阿斯巴甜引起的血浆氨基酸和脑血清素变化不足以导致可能促进戊四氮诱发癫痫发作的功能缺陷。
