DOPAMINE GLUTAMATE INTERACTIONS IN PARKINSONS-DISEASE/

In Parkinson's disease, the tonic inhibition by basal ganglia output s tructures may be exacerbated by the action of the subthalamic nucleus. As expected, the reduction of excitatory impact from this structure h as been shown to reduce akinesia in monkeys with experimental parkinso nism. The findings of receptor binding studies supporting an increased neuronal activity of efferents of the subthalamic nucleus in patients with Parkinson's disease, suggest that subthalamic nucleotomy or pall idotomy may be effective lesions in the neurosurgical treatment of Par kinson's disease. Systemic administration of glutamate antagonists has been shown to have anti-akinetic effects in animal models of Parkinso n's disease. Other observations in monkeys indicate that excitatory am ino acids such as glutamate are involved in the pathophysiological cas cade of MPTP ethyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced neuron al cell death. The neuroprotective effects of competitive and non-comp etive NMDA (N-methyl-D-aspartate) receptor antagonists against MPTP to xicity support the hypothesis that NMDA receptor-mediated events are i nvolved in the neurotoxicity of MPTP. Glutamate antagonists may theref ore be able to retard the progression and to improve the symptomatolog y of Parkinson's disease. Several compounds with anti-parkinsonian eff ects such as amantadine, memantine, budipine and orphenadrine have bee n shown to be non-competitive NMDA receptor antagonists and are candid ates for clinical trials on the neuroprotective efficacy of NMDA recep tor antagonism. Furthermore, glutamate antagonists are useful in the t reatment of the akinetic parkinsonian crisis, a severe form of clinica l deterioration in patients with Parkinson's disease. (C) 1997 Elsevie r Science Ltd.