The competitive NMDA antagonist CPP protects substantia nigra neurons from MPTP-induced degeneration in primates

Naunyn Schmiedebergs Arch Pharmacol. 1993 Dec;348(6):586-92. doi: 10.1007/BF00167234.

Abstract

Degeneration of nigrostriatal dopaminergic neurons is the primary histopathological feature of Parkinson's disease. The neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces a neurological syndrome in man and non-human primates very similar to idiopathic Parkinson's disease by selectively destroying dopaminergic nigrostriatal neurons. This gives rise to the hypothesis that Parkinson's disease may be caused by endogenous or environmental toxins. Endogenous excitatory amino acids (EAAs) such as L-glutamate could be involved in neurodegenerative disorders including Parkinson's disease. We report in this study that the competitive NMDA antagonist CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) protects nigral tyrosine hydroxylase (TH) positive neurons from degeneration induced by systemic treatment with MPTP in common marmosets. This indicates that EAAs are involved in the pathophysiological cascade of MPTP-induced neuronal cell death and that EAA antagonists may offer a neuroprotective therapy for Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Biogenic Monoamines / metabolism
  • Callithrix
  • Female
  • Immunohistochemistry
  • MPTP Poisoning*
  • Male
  • N-Methylaspartate / antagonists & inhibitors*
  • Nerve Degeneration / drug effects
  • Neurons / drug effects*
  • Neurons / enzymology
  • Piperazines / pharmacology*
  • Putamen / drug effects
  • Putamen / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Substantia Nigra / cytology
  • Substantia Nigra / drug effects*
  • Substantia Nigra / enzymology
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Biogenic Monoamines
  • Piperazines
  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • Tyrosine 3-Monooxygenase