Administration of aspartame potentiates pentylenetetrazole- and fluorothyl-induced seizures in mice.
An association has recently been proposed between the incidence of seizures and prolonged consumption of the phenylalanine-containing artificial sweetener, aspartame. Since consumption of aspartame, unlike dietary protein, can elevate phenylalanine in brain, and thereby inhibit the synthesis and release of neurotransmitters known to protect against seizure activity, the effect of oral doses of aspartame on the sensitivity of mice to the proconvulsant agents, pentylenetetrazole and fluorothyl was studied. Doses of aspartame were used which increased phenylalanine more than tyrosine in brain, as occurs in humans after the consumption of any dose of aspartame. Pretreatment with aspartame significantly increased the percentage of animals convulsing after administration of pentylenetetrazole and significantly lowered the CD50 for this convulsant. The average time to onset of seizures induced by fluorothyl in control mice was 510 sec; pretreatment with oral doses of 1000, 1500 and 2000 mg/kg of aspartame 1 hr earlier significantly reduced the time required to elicit seizures (394, 381 and 339 sec, respectively). The seizure-promoting effect of aspartame could be demonstrated 30, 60 or 120 min after the 1000 mg/kg dose. The seizures induced by either convulsant were potentiated by equimolar amounts of phenylalanine, a major endogenous metabolite of aspartame, while the other metabolites, aspartic acid and methanol, were without effect. Administration together with aspartame of the large neutral amino acid valine, which competes with phenylalanine for entry into the brain, completely abolished the seizure-promoting effect of aspartame.(ABSTRACT TRUNCATED AT 250 WORDS)
Pinto
J M
JM
Department of Pharmacology, Massachusetts College of Pharmacy, Boston 02115.
Maher
T J
TJ
D000818:Animals; D001218:Aspartame / Q000633:toxicity*; D004151:Dipeptides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005481:Flurothyl / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000494:pharmacology*; D010649:Phenylalanine / Q000097:blood; D012640:Seizures / Q000139:chemically induced*; D014443:Tyrosine / Q000097:blood
D004151:Dipeptides; D014443:Tyrosine; D010649:Phenylalanine; D005481:Flurothyl; D010433:Pentylenetetrazole; D001218:Aspartame