The role of glutamatergic neurotransmission in the motor and non-motor symptoms in Parkinson's disease: Clinical cases and a review of the literature
Por:
Pagonabarraga, J, Tinazzi, M, Caccia, C, Jost, WH
Publicada:
1 ago 2021
Ahead of Print:
1 jun 2021
Resumen:
Glutamate is the major excitatory neurotransmitter in the central nervous system and, as such, many brain regions, including the basal ganglia, are rich in glutamatergic neurons. The importance of the basal ganglia in the control of voluntary movement has long been recognised, with the effect of dysfunction of the region exemplified by the motor symptoms seen in Parkinson's disease (PD). However, the basal gan-glia and the associated glutamatergic system also play a role in the modulation of emotion, nociception and cognition, dysregulation of which result in some of the non-motor symptoms of PD (depression/anx-iety, pain and cognitive deficits). Thus, while the treatment of PD has traditionally been approached from the perspective of dopaminergic replacement, using agents such as levodopa and dopamine receptor ago-nists, the glutamatergic system offers a novel treatment target for the disease. Safinamide has been approved in over 20 countries globally for fluctuating PD as add-on therapy to levodopa regimens for the management of 'off' episodes. The drug has both dopaminergic and non-dopaminergic pharmacolog-ical effects, the latter including inhibition of abnormal glutamate release. The effect of safinamide on the glutamatergic system might present some advantages over dopamine-based therapies for PD by provid-ing efficacy for motor (levodopa-induced dyskinesia) as well as non-motor (anxiety, mood disorders, pain) symptoms. In this article, we discuss the potential role of glutamatergic inhibition on these symp-toms, using illustrative real-world examples of patients we have treated with safinamide. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
Filiaciones:
Pagonabarraga, J:
Hosp Santa Creu & Sant Pau, Dept Neurol, Movement Disorders Unit, Barcelona, Spain
Tinazzi, M:
Univ Verona, Dept Neurosci Biomed & Movement, Neurol Unit, Verona, Italy
Caccia, C:
CNS Preclin Pharmacol, Milan, Italy
Jost, WH:
Parkinson Klin Ortenau, Wolfach, Germany
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