[Action mechanism of L-dopa: dopaminergic activation or glutamatergic inhibition?]

Since 25 years ago, it was postulated that the antiparkinsonian activity of L-DOPA was due to the activation of the synthesis and the release of dopamine that it could trigger in the dopaminergic terminals preserved during the Parkinson's disease. Recent experimental data, presented in this paper could show that L-DOPA, far from activate the nigro-striatal dopaminergic neurons, would rather inhibit them and that its antiparkinsonian action could be attributed to the antiglutamatergic activity that L-DOPA, converted to dopamine, could exert by acting on the D2 receptors of the striatal glutamatergic afferences. This antiglutamatergic action of L-DOPA would concern the NMDA as well as the non-NMDA receptors and it is therefore unlikely that the NMDA antagonists could be good anti-parkinsonian drugs (unless they would be coadministered with non-NMDA antagonists). Dopaminergic (D2) agonists could be interesting antiparkinsonian drugs all the more they could be devoid of the potentially neurotoxic properties of L-DOPA.