Impairment of serotonergic transmission by the antiparkinsonian drug L-DOPA: Mechanisms and clinical implications

Cristina Miguelez, Abdelhamid Benazzouz, Luisa Ugedo, Philippe De Deurwaerdère
Front. Cell. Neurosci.. 2017-09-12; 11:
DOI: 10.3389/fncel.2017.00274

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The link between the anti-Parkinsonian drug L-3,4-dihydroxyphenylalanine (L-DOPA)
and the serotonergic (5-HT) system has been long established and has received
increased attention during the last decade. Most studies have focused on the fact
that L-DOPA can be transformed into dopamine (DA) and released from 5-HT
terminals, which is especially important for the management of L-DOPA-induced
dyskinesia. In patients, treatment using L-DOPA also impacts 5-HT
neurotransmission; however, few studies have investigated the mechanisms of this
effect. The purpose of this review is to summarize the electrophysiological and
neurochemical data concerning the effects of L-DOPA on 5-HT cell function. This
review will argue that L-DOPA disrupts the link between the electrical activity
of 5-HT neurons and 5-HT release as well as that between 5-HT release and
extracellular 5-HT levels. These effects are caused by the actions of L-DOPA and
DA in 5-HT neurons, which affect 5-HT neurotransmission from the biosynthesis of
5-HT to the impairment of the 5-HT transporter. The interaction between L-DOPA
and 5-HT transmission is especially relevant in those Parkinson’s disease (PD)
patients that suffer dyskinesia, comorbid anxiety or depression, since the
efficacy of antidepressants or 5-HT compounds may be affected.


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