Properties of 3-methyl-TIQ and 3-methyl-N-propargyl-TIQ for preventing MPTP-induced parkinsonism-like symptoms in mice.
Journal Title: Pharmacological Reports - Year 2013, Vol 65, Issue 5
Abstract
Background: Selegiline, a therapeutic drug for Parkinson's disease (PD), structurally resembles the endogenous parkinsonism-related compound 1,2,3,4-tetrahydroisoquinoline (TIQ). In the present study, we evaluated the effects of 3-methyl-TIQ (3-MeTIQ) and 3-methyl-N-propargyl-TIQ (3-Me-N-proTIQ), selegiline mimetic TIQ derivatives, for preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism-like symptoms in mice. Methods: We evaluated the preventative effects of 3-MeTIQ and 3-Me-N-proTIQ on MPTP-induced bradykinesia and depletion of striatal dopamine (DA) and nigral tyrosine hydroxylase (TH)-positive cells. Results: MPTP-induced bradykinesia was not different when mice were pretreated with 3-MeTIQ, except for the high-dose group. However, pretreatment with 3-Me-N-proTIQ significantly prevented the appearance of this akinesic status. MPTP-induced striatal DA and 3,4-dehydroxyphenylacetic acid reduction were significantly prevented by pretreatment with 3-Me-N-proTIQ, but not 3-MeTIQ, in a dose-dependent manner. On the other hand, levels of serotonin and its metabolite, 5-hydroxyindole acetic acid, in the striatum were increased following treatment with 3-MeTIQ. In addition, the MPTP-induced decrease in TH-positive cells in the substantia nigra was significantly reduced by pretreatment with 3-Me-N-proTIQ, but not 3-MeTIQ. Conclusions: These results suggest that not only does 3-Me-N-proTIQ have potential as a candidate compound for disease-modifying therapy for PD, but also the N-propargyl functional group plays an important role in neuroprotection.
Authors and Affiliations
Kanako Saitoh, Kenji Abe, Terumasa Chiba, Nobuyuki Katagiri, Toshiaki Saitoh, Yoshie Horiguchi, Hiroshi Nojima, Kyoji Taguchi
Keywords
Related Articles
- EP ID EP152034
- DOI -
- Views 91
- Downloads 0
Effects of bestatin on phagocytic cells in cyclophosphamide-treated mice.
The low-molecular weight dipeptide bestatin is a potent inhibitor of aminopeptidase N and has been demonstrated to have antitumor and immunomodulatory effects. The effects of bestatin on interleukin (IL)-1β synthesis and...
Antinociception after intrathecal biphalin application in rats: a reevaluation and novel, rapid method to confirm correct catheter tip position.
The opioid peptide dimmer biphalin [(Tyr-D-Ala-Gly-Phe-NH-)(2)] has high potency both in vivo and in vitro. Its antinociceptive activity depends on the route of administration: the lowest potency is after subcutaneous, a...
Analgesic activity of 3-mono-substituted derivatives of dihydrofuran-2-one in experimental rodent models of pain.
Three derivatives of dihydrofuran-2-one (L-PP, L-PP1, and L-SAL) were administered by intraperitoneal injection and their analgesic activity was assayed in several models of pain. The activity of these derivatives were t...
Repeated co-treatment with fluoxetine and amantadine induces brain-derived neurotrophic factor gene expression in rats.
In the present study, we investigated the influence of repeated treatment with fluoxetine (FLU, 5 or 10 mg/kg) and amantadine (AMA, 10 mg/kg), given separately or jointly (twice daily for 14 day), at the mRNA level (the...
Influence of bupropion and calcium channel antagonists on the nicotine-induced memory-related response of mice in the elevated plus maze.
In this study, we investigated the effects of acute administration of nicotine on memory-related behavior in mice using the elevated plus maze test. In this test, the time necessary for mice to move from the open arm to...