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Anti-Parkinson Activity

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Drug Discovery and Evaluation: Pharmacological Assays

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Abstract

In humans, Parkinson’s disease is characterized by fixed facial expression, tremor at rest, slowing of voluntary movements, impaired gait, impaired posture, and muscle weakness. A fundamental lesion in Parkinson’s disease produces a marked deficiency in the dopaminergic innervation of the basal ganglia due to degeneration of neurons in the substantia nigra. Enhancement of dopaminergic transmission restores motor function at least partially. The decrease in dopaminergic activity in the basal ganglia results in a relative excess of cholinergic influence. Therefore, dopaminergic agonists, such as levodopa a precursor of dopamine, and cholinergic (muscarinic) antagonists can be combined in the treatment of Parkinson’s disease. Enhancement of dopaminergic activity wanes with repeated treatment with dopaminergic agonists over time. Parkinson-like syndromes also occur after depletion of central stores by reserpine and after treatment with phenothiazines and other antipsychotic drugs blocking dopamine receptors (Vernier 1964; Marsden et al. 1975; Duvoisin 1976; Hornykiewicz 1975; Miller and Hiley 1975). The pathology of Parkinson’s disease is typified by the presence of cytoplasmic inclusions (Lewy bodies). The formation of these proteinaceous inclusions involves the interaction of several proteins, including α-synuclein, synphilin, parkin, and ubiquitin carboxyl-terminal hydrolases (Goldberg and Lansbury 2000; Shimohama et al. 2003; Le and Appel 2004; Meredith et al. 2004; Snyder and Wolozin 2004; von Bohlen und Halbach et al. 2004). Orr et al. (2002) gave a review on inflammatory aspects of Parkinson’s disease and highlighted the cell-to-cell interactions and immune regulations critical for neuronal homeostasis and survival. Parkinson’s disease and related synucleinopathies are considered as a new class of nervous system amyloidoses (Trojanowski and Lee 2002; Dev et al. 2004; Liu et al. 2005). None of the currently available preclinical Parkinson’s disease models characterize all of the observed human symptoms of the disease (Valadas et al. 2015). The lack of consistency between the human situation and the animals models may result from the diverse risk factors associated with the occurrence of Parkinson’s disease. Only 10 % or less of cases are associated with a genetic link, while the majority of are sporadic (Johnson and Bobrovskaya 2015).

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    Mary-Jeanne Kallman

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    Franz J. Hock

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Kallman, MJ. (2015). Anti-Parkinson Activity. In: Hock, F. (eds) Drug Discovery and Evaluation: Pharmacological Assays. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27728-3_32-2

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  • DOI: https://doi.org/10.1007/978-3-642-27728-3_32-2

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  1. Latest

    Anti-Parkinson Activity
    Published:
    03 March 2016

    DOI: https://doi.org/10.1007/978-3-642-27728-3_32-2

  2. Original

    Anti-Parkinson Activity
    Published:
    21 July 2015

    DOI: https://doi.org/10.1007/978-3-642-27728-3_32-1

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