Zusammenfassung
Glutamate is the most important excitatory neurotransmitter in the mammalian brain. Recent findings suggest that dopamine is of less importance in the regulation of psychomotor functions than was previously believed. Central glutamatergic dysfunction appears to play a significant role in movement disorders and schizophrenia. An imbalance between dopaminergic and glutamatergic mechanisms is ...
Zusammenfassung
Glutamate is the most important excitatory neurotransmitter in the mammalian brain. Recent findings suggest that dopamine is of less importance in the regulation of psychomotor functions than was previously believed. Central glutamatergic dysfunction appears to play a significant role in movement disorders and schizophrenia. An imbalance between dopaminergic and glutamatergic mechanisms is probably responsible for both akinetic motor disturbances and psychosis. Animal experiments suggest that in Parkinson's disease there exists a glutamatergic overactivity within the basal ganglia and that a selective reduction of glutamatergic function may be of therapeutic benefit in Parkinsonian patients. Drugs with glutamate antagonistic properties can counteract glutamatergic overactivity in Parkinson's disease. The noncompetitive N-methyl-D-aspartate (NMDA) antagonists amantadine and memantine have symptomatic effects and improve akinesia and rigidity. Recent findings in animals suggest that glutamate may be involved in the pathogenesis of Parkinson's disease and that NMDA antagonists may have neuroprotective effects. The administration of NMDA antagonists such as amantadine together with L-dopa in Parkinson's disease could have neuroprotective effects, since co-administration decreases the L-dopa dose needed and this can reduce the toxic consequences of dopamine metabolism such as oxidative stress, lipid peroxidation and membrane damage. Recent evidence suggests that decreased glutamatergic neurotransmission may play a role in the pathophysiology of schizophrenia. There exists in the striatum a functional antagonism between glutamatergic and dopaminergic systems. It is therefore possible that there is no absolute dopaminergic hyperactivity in the brain of schizophrenic patients but rather a glutamatergic hypoactivity.
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