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  • Evaluation of behavioural effects of a selective NMDA NR1A/2B receptor antagonist in the unilateral 6-OHDA lesion rat model

    Author(s)
    Warraich, ST
    Allbutt, HN
    Billing, R
    Radford, J
    Coster, MJ
    Kassiou, M
    Henderson, JM
    Griffith University Author(s)
    Coster, Mark J.
    Year published
    2009
    Metadata
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    Abstract
    The degeneration of the dopaminergic nigrostriatal pathway in Parkinson's disease (PD) is associated with altered transmission at striatal NMDA receptors containing NR2B subunits. We investigated a potential novel therapeutic compound, 4-trifluoromethoxy-N-(2-trifluoromethyl-benzyl)-benzamidine (BZAD-01), a selective NMDA NR1A/2B receptor antagonist for PD and compared it with levodopa, the standard treatment for PD. This study also evaluated whether combining levodopa and BZAD-01 gave better improvements of parkinsonian symptoms. Parkinsonism was induced by microinjection of the toxin, 6-hydroxydopamine (6-OHDA) into the ...
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    The degeneration of the dopaminergic nigrostriatal pathway in Parkinson's disease (PD) is associated with altered transmission at striatal NMDA receptors containing NR2B subunits. We investigated a potential novel therapeutic compound, 4-trifluoromethoxy-N-(2-trifluoromethyl-benzyl)-benzamidine (BZAD-01), a selective NMDA NR1A/2B receptor antagonist for PD and compared it with levodopa, the standard treatment for PD. This study also evaluated whether combining levodopa and BZAD-01 gave better improvements of parkinsonian symptoms. Parkinsonism was induced by microinjection of the toxin, 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) of 40 Sprague-Dawley rats. Parkinsonism and the efficacy of drugs were assessed using a battery of behavioural tests including balance beam, apomorphine-induced rotation, body axis bias or "curling", head position bias and disengage sensorimotor latency test. Immunohistochemistry was performed on post-mortem tissue to estimate the loss of dopaminergic neurons. The main effects were that BZAD-01 co-administration prevented chronic levodopa-induced potentiation of apomorphine rotation. However levodopa-treated rats were slower than either controls or BZAD-01-treated rats in the locomotor test. The improvement in the apomorphine rotation test suggests that BZAD-01 may be a useful adjunct to levodopa monotherapy.
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    Journal Title
    Brain Research Bulletin
    Volume
    78
    Issue
    2-3
    DOI
    https://doi.org/10.1016/j.brainresbull.2008.08.023
    Subject
    Cell neurochemistry
    Neurosciences
    Cognitive and computational psychology
    Publication URI
    http://hdl.handle.net/10072/34344
    Collection
    • Journal articles

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