The anti-parkinsonian drug amantadine inhibits the N-methyl-D-aspartic acid-evoked release of acetylcholine from rat neostriatum in a non-competitive way

The anti-viral drug amantadine is used in the treatment of Parkinson's disease without the drug having a well established mechanism of action. Amantadine is reported to displace the non-competitive NMDA receptor antagonist MK-801 from its binding site in the central nervous system. We show 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 range) concentrations. Moreover, contrary to previous reports, amantadine, in this concentration range, did not affect the in vitro release of dopamine from neostriatal tissue.