Neuroprotective mechanism of modafinil on Parkinson disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Acta Pharmacol Sin. 2004 Mar;25(3):301-5.


Aim: To observe the neuroprotective mechanism of modafinil on Parkinson disease (PD) models induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP).

Methods: The model of PD was induced by intraperitoneally injecting MPTP into C57BL/6J mice for 4 d. Modafinil (i.p., 50 or 100 mg/kg(-1)/d(-1)) was administered at 30 min following MPTP for 4 d and for another 10 d continuously. The contents of dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA), glutamine (Glu) in the striatum, and the contents of GABA, Glu, malondialdehyde (MDA), and glutathione (GSH) in the substantia nigra (SN) of model mice were determined.

Results: Modafinil (50 and 100 mg/kg) prevented against the decrease of the contents of DA, 5-HT, and NA in the striatum and GSH, GABA in the SN induced by MPTP, but reduced the increase of MDA in the SN and GABA in the striatum induced by MPTP. Modafinil preferentially inhibited striatal GABA release, but it did not change the increase of nigrostriatal Glu release induced by MPTP.

Conclusion: The anti-oxidation and the modulation of nigrostriatal GABA and striatal NA and 5-HT release contributed to the neuroprotective effects of modafinil on PD induced by MPTP.

MeSH terms

  • Animals
  • Benzhydryl Compounds / pharmacology*
  • Corpus Striatum / metabolism
  • Dopamine / metabolism
  • MPTP Poisoning / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Modafinil
  • Neuroprotective Agents / pharmacology*
  • Norepinephrine / metabolism
  • Serotonin / metabolism
  • Substantia Nigra / metabolism*
  • gamma-Aminobutyric Acid / metabolism*


  • Benzhydryl Compounds
  • Neuroprotective Agents
  • Serotonin
  • gamma-Aminobutyric Acid
  • Modafinil
  • Dopamine
  • Norepinephrine