These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The monoamine oxidase-B inhibitor L-deprenyl protects against 3,4-methylenedioxymethamphetamine-induced lipid peroxidation and long-term serotonergic deficits.
    Author: Sprague JE, Nichols DE.
    Journal: J Pharmacol Exp Ther; 1995 May; 273(2):667-73. PubMed ID: 7538579.
    Abstract:
    3,4-Methylenedioxymethamphetamine (MDMA)-induced serotonergic neurotoxicity was assessed in the striatum, hippocampus and frontal cortex of rats by using [3H]paroxetine binding to label serotonin (5-HT) uptake sites and 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels as markers of serotonergic function. NMDA (40 mg/kg) induced a significant decrease in both [3H]paroxetine binding Bmax and 5-HT and 5-HIAA levels 7 days after treatment. The monoamine oxidase-B inhibitor L-deprenyl (2 mg/kg) administered 30 min before MDMA blocked these decreases. MDMA (40 mg/kg) also maximally increased the formation of thiobarbituric acid reactive substances (an indicator of lipid peroxidation) 12 hr after treatment in all three brain regions studied. This increase in malondialdehyde formation was also blocked by pretreatment with L-deprenyl. Tryptophan hydroxylase (TPH) activity was also significantly reduced 18 hr after MDMA. L-Deprenyl reversed this decrease in TPH activity. Another experiment confirmed that a significant fraction of [3H]dopamine uptake into hippocampal synaptosomes was blocked by 500 nM fluoxetine, a selective 5-HT uptake inhibitor. These data suggest that the deamination by monoamine oxidase-B of excessive dopamine within the 5-HT terminal generates hydrogen peroxide that may lead to membrane lipid peroxidation, and perhaps other oxidative insults, resulting in selective 5-HT terminal degeneration subsequent to MDMA treatment.
    [Abstract] [Full Text] [Related] [New Search]