Apparent antioxidant effect of l-deprenyl on hydroxyl radical formation and nigral injury elicited by MPP+ in vivo

Eur J Pharmacol. 1993 Oct 26;243(3):241-7. doi: 10.1016/0014-2999(93)90181-g.


Using a modified microdialysis procedure, we confirmed that intrastriatal administration of 1-methyl-4-phenylpyridinium ion (MPP+) induced a sustained overflow of dopamine accompanied by increased formation of hydroxyl free radicals (.OH) as reflected by salicylate hydroxylation. Pretreatment with l-deprenyl (selegiline 60 pmol, intrastriatal perfusion) significantly decreased the .OH formation elicited by MPP+ (75 nmol). There was a small decrease of dopamine efflux and an insignificant change of the ratio of 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine following l-deprenyl pretreatment. These in vivo findings support prior in vitro data that an unique antioxidant property of l-deprenyl may be independent of its inhibition of type B monoamine oxidase. In addition, intranigral co-administration of l-deprenyl (4.2 nmol) with MPP+ (4.2 nmol) completely protected nigral neurons from probable oxidative injuries induced by MPP+ (4.2 nmol), as reflected by a near 50% loss of striatal dopamine ipsilateral to the side of infusion of drug into the substantia nigra. This apparent neuroprotective effect of l-deprenyl on midbrain nigral neurons was also confirmed by histological findings. The present in vivo data clearly demonstrate that l-deprenyl can protect nigral neurons against dopamine neurotoxicity produced by MPP+, as suggested by an earlier in vitro study. Thus, l-deprenyl can preserve the function of MPP(+)-damaged nigral neurons perhaps by its apparent antioxidant property in addition to its blockade of the bioactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to toxic pyridinium metabolites by type B monoamine oxidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / antagonists & inhibitors
  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Animals
  • Antioxidants / pharmacology*
  • Dopamine / metabolism
  • Hydroxyl Radical / metabolism*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Selegiline / pharmacology*
  • Substantia Nigra / drug effects*


  • Antioxidants
  • Selegiline
  • Hydroxyl Radical
  • 1-Methyl-4-phenylpyridinium
  • Dopamine