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: A simple rodent assay for the in vivo identification of agents with potential to reduce levodopa-induced dyskinesia in Parkinson's disease.
    Author: Johnston TH, Lee J, Gomez-Ramirez J, Fox SH, Brotchie JM.
    Journal: Exp Neurol; 2005 Feb; 191(2):243-50. PubMed ID: 15649479.
    Abstract:
    l-DOPA-induced dyskinesia (LID) remains a major complication of the treatment of Parkinson's disease (PD). Whilst the MPTP-lesioned primate provides an excellent animal model in which to develop new therapies, however, it is logistically difficult to employ widely. Thus, a simple rodent assay to screen multiple compounds as candidates for further study of their potential in LID would be a valuable addition to the drug development process. Here, we investigate how agents with demonstrated ability to reduce LID in man and monkey can regulate l-DOPA-induced behaviours in the reserpine-treated rat. Administration of l-DOPA (125 mg/kg) to reserpine-treated rats elicited high levels of both horizontal and vertical movement. Drugs that have previously been found to reduce LID in parkinsonian primates and PD patients without compromising the anti-parkinsonian efficacy of l-DOPA selectively and dose-dependently reduce vertical components of activity when co-administered with l-DOPA in the reserpine-treated rat. For instance, amantadine (1 mg/kg) and idazoxan (3 mg/kg) reduced vertical activity by 59% and 83%, respectively, while neither drug had significant effects on horizontal activity. In contrast, haloperidol (1 mg/kg), an agent lacking the ability to selectively reduce LID without compromising the anti-parkinsonian actions of l-DOPA, reduced both horizontal and vertical activity, by 98% and 99%, respectively. We also assessed the actions of an NMDA antagonist, a class of compound proposed to have potential as anti-dyskinetic agents. The effects of MK-801 were dose-dependent (0.01-0.5 mg/kg), at some doses (e.g., 0.05 mg/kg), providing selective reduction of vertical activity (90%), at others (e.g., 0.5 mg/kg), non-selective reduction of vertical and horizontal (99% and 77%, respectively). These observations highlight the association between potential anti-dyskinetic action and a selective reduction in l-DOPA-induced vertical activity in the reserpine-treated rat.
    [Abstract] [Full Text] [Related] [New Search]