[Current preclinical findings on substances against Parkinson's disease].
Striatal dopamine loss provides the premise for dopamine substitution in palliative therapy for Parkinson's disease (PD). This includes firstly L-dopa (L-3,4-dihydroxyphenylalanine, levodopa) and dopamine receptor agonists. Although this therapy has been demonstrated to induce marked clinical improvement in the early stages of PD, its use is limited in the long term by a loss of efficacy. In addition, most patients develop the "long-term L-dopa syndrome," which is characterized by a decrease in the control of Parkinsonian symptoms (decrease in the drug's effect) and the appearance of certain motor disturbances including episodes of akinetic freezing, debilitating dyskinesias, and on-off periods. The aim in developing new drugs is to achieve better therapeutic approaches. In the case of PD, the main strategies are to develop (1) alternatives to L-dopa therapy for alleviating the striatal dopamine deficit while avoiding or retarding the long-term L-dopa syndrome, (2) antidyskinetic approaches, and (3) neuroprotective drugs aimed at causal treatment of PD which is able to preserve the remaining dopaminergic neurones and to halt or at least retard the disease process. This article reviews new approaches for the treatment of PD and presents findings from our studies using a new experimental in vivo model of PD.
Gerlach
M
M
Klinische Neurochemie, Universitätsklinik für Psychiatrie und Psychotherapie, Würzburg. manfred.gerlach@mail.uni-wuerzburg.de
Riederer
P
P
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017173:Caenorhabditis elegans; D003342:Corpus Striatum / Q000187:drug effects; D018491:Dopamine Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy*; D020734:Parkinsonian Disorders / Q000188:drug therapy*
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D015507:Drugs, Investigational; D018696:Neuroprotective Agents; D007980:Levodopa