Antiparkinsonian drugs and in vitro excitotoxicity

N-Methyl-D-aspartate (NMDA) receptor activation has been implicated in the pathogenesis and clinical expression of Parkinson's disease. Because some antiparkinsonian drugs have NMDA antagonist properties, we examined their effects on NMDA toxicity, measured by lactate dehydrogenase (LDH) release, in neuron-enriched cerebrocortical cultures. Amantadine reduced NMDA toxicity with half-maximal reduction at approximately 30 microM, while trihexphenidyl, L-3,4-dihydroxyphenylalanine (L-DOPA), bromocriptine and selegiline were ineffective, and benztropine was itself toxic. Amantadine and related drugs could not only reduce parkinsonian symptoms, but also modify underlying neurodegenerative processes.