NEW DEVELOPMENTS IN NEUROLOGY

Although the aetiology of Parkinson's disease remains unknown, an impr oved understanding of the neurobiology of Parkinson's disease has open ed up new avenues for pharmacological therapeutic interventions. Some of these new neuropharmacological approaches are still in the experime ntal preclinical phase, whereas others are currently studied in patien ts. In addition, experimental neuropharmacological research provides a better understanding of the mechanism of action of conventional antip arkinsonian drugs. Recent experimental evidence suggests that striatal dopamine loss leads to increased glutamatergic transmission in the ba sal ganglia. In animal experiments, the action of L-dopa and dopamine agonists is potentiated by glutamate antagonists. A number of weak glu tamate antagonists with low specificity are available for clinical use . These compounds include amantadine, memantine and budipine. Neurotro phic factors, such as ciliary neurotrophic factor (CNTF) and glial cel l line derived neurotrophic factor (GDNF) are promising new approaches for neuroprotection in Parkinson's disease. Problems of bioavailabili ty thus far preclude their use in patients. Catechol-O-methyl-transfer ase (COMT) inhibitors are a new class of drugs that act on the dopamin ergic system. Clinical studies show that COMT inhibitors prolong the a ction of L-dopa in patients with wearing off phenomenon. In spite of i ts haematological risk, the atypical neuroleptic clozapine is the trea tment of choice for the alleviation of L-dopa-induced psychosis. Cloza pine has also beneficial effects on tremor and L-dopa-induced dyskines ias. The monoamine oxidase B (MAO-B) inhibitor deprenyl blocks the oxi dative metabolism of dopamine and reduces the formation of free oxygen radicals. On the basis of these properties neuroprotective actions of deprenyl have been postulated. Clinical studies, however, failed to u ndoubtedly prove a neuroprotective action of deprenyl in patients. New experimental studies show protective actions of deprenyl, which are i ndependent of MAO-B inhibition and which are due to a direct effect on gene transcription.