Effects of glutamate antagonists on the activity of aromatic L-amino acid decarboxylase.

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Fisher A, Biggs CS, Starr MS

Effects of glutamate antagonists on the activity of aromatic L-amino acid decarboxylase.

Amino Acids. 1998;14(1-3):43-9.

PubMed ID

9871440 [ View in PubMed

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Abstract

This study examines the hypothesis that glutamate tonically suppresses the activity of the enzyme aromatic L-amino acid decarboxylase (AADC), and hence the biosynthesis of dopamine, to explain how antagonists of glutamate receptors might potentiale the motor actions of L-DOPA in animal models of Parkinson's disease. A variety of glutamate antagonists were therefore administered acutely to normal rats, which were sacrificed 30-60 min later and AADC activity assayed in the substantia nigra pars reticulata (SNr) and corpus striatum (CS). The NMDA receptor-ion channel antagonists MK 801, budipine, amantadine, memantine and dextromethorphan all caused a pronounced in creased in AADC activity, more especially in the SNr than CS. The NMDA glycine site antagonist (R)-HA 966 produced a modest increase in AADC activity in the CS but not SNr, whilst the NMDA polyamine site antagonist eliprodil, the NMDA competitive antagonist CGP 40116 and the AMPA antagonist NBQX were without effect. The results suggest that an increase in dopamine synthesis might contribute to the L-DOPA-facilitating actions of some glutamate antagonists.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Amantadine	Aromatic-L-amino-acid decarboxylase	Protein	Humans	Unknown	Inducer	Details