Amantadine as N-methyl-D-aspartic acid receptor antagonist: new possibilities for therapeutic applications?

J C Stoof, J Booij, B Drukarch

Research output: Contribution to journalArticleAcademicpeer-review


The N-methyl-D-aspartic acid (NMDA) receptor is an intriguing target for the development of drugs with anti-Parkinsonian activity as well as with protective actions against degenerative processes induced by brain ischemia. Amantadine is used in the treatment of Parkinson's disease without a well established mechanism of action. We show here that amantadine inhibits, in a non-competitive way, the NMDA receptor-mediated stimulation of acetylcholine release from rat neostriatum in vitro in "therapeutic" (i.e., low micromolar) concentrations. This indicates that amantadine might exert its anti-Parkinsonian effect via blockade of NMDA receptors. Sustained stimulation of NMDA receptors induces so-called excitotoxicity. Recently, it was demonstrated that amantadine is able to inhibit NMDA induced cell death in a neuronal culture. On the basis of these findings it seems worth investigating if amantadine is also able to protect against neurodegenerative processes caused by brain ischemia in vivo.

Original languageEnglish
Pages (from-to)S4-6
JournalClinical Neurology and Neurosurgery
Volume94 Suppl
Publication statusPublished - 1992

Cite this