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Drug Treatment of Motor Symptoms in Parkinson's Disease

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

Insidious onset of mild, unspecific, vegetative, psychopathological, cognitive, and perceptive disturbances with a resulting change in personal behavior often precede the initial intermittent onset of motor symptoms in patients with Parkinson's disease (PD). Currently available diagnostic tools and concepts suggest this appearance of motor symptoms as the criterion for diagnosis of PD. Motor symptom control can be achieved by dopaminergic substitution, which should deliver a dopamine‐substituting drug in a continuous fashion to the brain, This enables imitation of physiologic conditions of dopaminergic neurotransmission. This delays onset of motor complications which mostly appear after a certain period probably due to progression of the disease with loss of compensatory mechanisms, which reduce alternating levels of dopamine‐substituting compounds in the synaptic cleft and at striatal postsynaptic dopaminergic uptake sites. These long‐term motor complications are fluctuations of movement and are mostly associated with levodopa owing to the short half‐life of the drug. They considerably burden quality of life in PD patients and their caregivers. These complications follow the so‐called honeymoon period of well‐tolerated levodopa administration and are looked upon as one essential clinical marker of dopaminergic chronic neurodegeneration and progression in PD patients. Dopamine agonists delay onset of these motor complications because of their longer half‐life in plasma and their affinity to striatal postsynaptic dopaminergic uptake sites. However, their efficacy and tolerability differ in the individual patient and is generally reduced compared with levodopa. Dopaminergic substitution with dopamine agonists or MAO‐B inhibitors instead of levodopa also prevent levodopa‐associated homocysteine elevation which may contribute to progression of PD and increase the risk for onset of nonmotor features like dementia and depression in the long run. These nonmotor PD symptoms predominantly result from nondopaminergic neurodegeneration and additionally considerably reduce quality of life, in particular in advanced stages of the disease.

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Abbreviations

COMT:

catechol-O-methyltransferase

DDI:

decarboxylase inhibitor

DEC:

dihydroergocryptin

DIRD:

DA-induced respiratory disorders

GABA:

gamma-aminobutyric acid

MAO-B:

Monoaminooxidase-B

MAO:

monoaminooxidase

NMDA:

N-methyl-d-aspartate

PD:

Parkinson's disease

UPDRS:

Unified Parkinson's Disease Rating Scale

3-OMD:

3-O-methyldopa

5-HT:

serotonine

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Authors
  1. T. Müller
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, New York, 10962, Orangeburg, USA

    Abel Lajtha (Director) (Director)

  2. Technion‐Rappaport Family Faculty of Medicine, Efron St., POBox 9697, 31096, Haifa, Israel

    Moussa B. H. Youdim (Professor of Pharmacology Professor of Life Sciences Director of Eve Topf and NPF Centers of Excellence for Neurodegenerative Diseases Research) (Professor of Pharmacology Professor of Life Sciences Director of Eve Topf and NPF Centers of Excellence for Neurodegenerative Diseases Research)

  3. Clinic and Policlinic of Psychiatry and Psychotherapy Dept. Clinical Neurochemistry, University of Würzburg, Füchsleinstr. 15, 97080, Würzburg, Germany

    Peter Riederer

  4. Eve Topf Center for Neurodegenerative Diseases Research and Dept. of Pharmacology, Faculty of Medicine Technion, Efron St., P.O.B. 9697, 31096, Haifa, Israel

    Sylvia A. Mandel

  5. Department of Neurosciences, University of Padova Medical School, Via Giustiniani 5, 35128, Padova, Italy

    Leontino Battistin

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Müller, T. (2007). Drug Treatment of Motor Symptoms in Parkinson's Disease. In: Lajtha, A., Youdim, M.B.H., Riederer, P., Mandel, S.A., Battistin, L. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30377-2_7

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