| Abstrakt: |
The pharmacotherapy of Parkinson's disease mainly consists of treatment with levodopa and/or dopamine receptor agonists, which compensate for the loss of dopamine in the CNS that characterises the disease. Although treatment with levodopa is more effective than that with dopamine receptor agonists, the former frequently causes serious adverse effects, e.g. wearing-off phenomena and dyskinesias. Levodopa (after conversion to dopamine) stimulates dopamine D and D receptors, whereas the presently available dopamine agonists act mainly on D receptors. Therefore, the D receptor might be a potential target for pharmacotherapy in Parkinson's disease. However, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkey model of Parkinson's disease, the partial D agonist SKF-38393 failed to stimulate motor behaviour. Newly developed agents that are full agonists at the D receptor do stimulate motor behaviour of MPTP-lesioned monkeys and act synergistically with D receptor agonists. Nonetheless, several of these compounds lose their efficacy in stimulating motor behaviour upon sustained administration and induce dyskinetic behaviour. Moreover, these compounds are likely to have the potential to induce epileptic seizures. Therefore, the potential value of the newly developed D receptor agonists in the treatment of Parkinson's disease seems limited. [ABSTRACT FROM AUTHOR] |
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