Glutamate-dopamine interactions in the basal ganglia: relationship to Parkinson's disease.
Current antiparkinsonian therapies focus on either replacing dopamine via precursor (L-DOPA) administration, or directly stimulating post-synaptic dopamine receptors with dopamine agonists. Unfortunately, this approach is associated with numerous side effects and these drugs lose efficacy with disease progression. This article reviews recent evidence which suggests that negative modulation of glutamatergic neurotransmission has antiparkinsonian effects in a variety of rodent and primate models of parkinsonism. The pronounced synergism between dopaminergic agents and glutamate receptor antagonists may provide a means of using very low doses of the two drug classes in concert to treat Parkinson's disease effectively and minimize dose-related drug side effects.
Greenamyre
J T
JT
Department of Neurology, University of Rochester, NY.
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001479:Basal Ganglia / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000627:therapeutic use; D004298:Dopamine / Q000172:deficiency / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004361:Drug Tolerance; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D000882:Haplorhini; D006801:Humans; D020267:MPTP Poisoning; D051379:Mice; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology*; D010302:Parkinson Disease, Secondary / Q000188:drug therapy / Q000503:physiopathology; D011810:Quinoxalines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D011810:Quinoxalines; D011954:Receptors, Dopamine; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D016627:Oxidopamine; D004298:Dopamine