Deprenyl protects dopamine neurons from the neurotoxic effect of 1-methyl-4-phenylpyridinium ion

J Neurochem. 1985 Dec;45(6):1951-3. doi: 10.1111/j.1471-4159.1985.tb10556.x.

Abstract

1-Methyl-4-phenylpyridinium ion (MPP+) is the product of the metabolic oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by monoamine oxidase (MAO). MPP+ is toxic to 3,4-dihydroxyphenylethylamine (dopamine, DA) neurons in explant cultures of rat embryonic midbrain. Addition of 2.5 microM MPP+ to the feeding medium for 6 days results in significant reduction of the DA levels in the cultures (to 19% of control) as well as in the uptake of [3H]DA (to 32% of control). When the cultures are treated with the MAO inhibitor deprenyl (10 microM) 24 h prior to and during exposure to MPP+, the DA neurons are protected from the toxicity of the drug. In the combined deprenyl plus MPP+ treatment, the levels of DA in the cultures remain at the control range and the [3H]DA uptake is reduced to only 73% of control. These results indicate that MAO is involved in the toxicity of MPP+ on DA neurons.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1-Methyl-4-phenylpyridinium
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Neurons / drug effects*
  • Phenethylamines / pharmacology*
  • Pyridines / metabolism
  • Pyridinium Compounds / pharmacology*
  • Rats
  • Selegiline / pharmacology*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism

Substances

  • Phenethylamines
  • Pyridines
  • Pyridinium Compounds
  • Selegiline
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1-Methyl-4-phenylpyridinium
  • Dopamine