Methamphetamine protects against MPTP neurotoxicity in C57BL mice.
Methamphetamine (5 mg/kg) administered 30 min prior to each injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (3 x 30 mg/kg, at 24 h intervals) prevents the reduction of striatal levels of dopamine and its metabolites in C57BL mice. Methamphetamine and amphetamine inhibit the uptake of 1-methyl-4-phenylpyridinium (MPP+) by striatal synaptosomes of rats. A 30-min post-treatment with methamphetamine or amphetamine also prevents the MPTP-induced dopamine depletion, suggesting that their protective effect is related to the blockade of MPP+ uptake into dopaminergic neurons. Since amphetamine and methamphetamine are themselves neurotoxins at higher doses, this work demonstrated the protection against the actions of one neurotoxin by the administration of another.
Sziráki
I
I
Division of Biochemistry, Institute for Drug Research, Budapest, Hungary.
Kardos
V
V
Patthy
M
M
Pátfalusi
M
M
Budai
G
G
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism / Q000493:pharmacokinetics; D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism / Q000493:pharmacokinetics; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D020267:MPTP Poisoning; D008297:Male; D008694:Methamphetamine / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism
D008694:Methamphetamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000661:Amphetamine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine