Functional efficacy of the MAO-B inhibitor safinamide in murine substantia nigra pars compacta dopaminergic neurons in vitro: A comparative study with tranylcypromine.

Autor: Zarrilli B; Department of Experimental Neuroscience, Santa Lucia Foundation IRCCS, Via del Fosso di Fiorano, 64, 00143, Rome, Italy; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA., Giacomet C; Department of Experimental Neuroscience, Santa Lucia Foundation IRCCS, Via del Fosso di Fiorano, 64, 00143, Rome, Italy; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA., Cossa F; Department of Experimental Neuroscience, Santa Lucia Foundation IRCCS, Via del Fosso di Fiorano, 64, 00143, Rome, Italy; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA., Federici M; Department of Experimental Neuroscience, Santa Lucia Foundation IRCCS, Via del Fosso di Fiorano, 64, 00143, Rome, Italy; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA., Berretta N; Department of Experimental Neuroscience, Santa Lucia Foundation IRCCS, Via del Fosso di Fiorano, 64, 00143, Rome, Italy; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA. Electronic address: n.berretta@hsantalucia.it., Mercuri NB; Department of Experimental Neuroscience, Santa Lucia Foundation IRCCS, Via del Fosso di Fiorano, 64, 00143, Rome, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA. Electronic address: mercurin@med.uniroma2.it.
Jazyk: angličtina
Zdroj: Parkinsonism & related disorders [Parkinsonism Relat Disord] 2024 Nov; Vol. 128, pp. 107158. Date of Electronic Publication: 2024 Sep 21.
DOI: 10.1016/j.parkreldis.2024.107158
Abstrakt: Safinamide (SAF) is currently used to treat Parkinson's disease (PD) symptoms based on its theoretical ability to potentiate the dopamine (DA) signal, blocking monoamine oxidase (MAO) B. The present work aims to highlight the functional relevance of SAF as an enhancer of the DA signal, by evaluating its ability to prolong recovery from DA-mediated firing inhibition of DAergic neurons of the substantia nigra pars compacta (SNpc), compared to another MAO antagonist, tranylcypromine (TCP). Using multielectrode array (MEA) and single electrode extracellular recordings of spontaneous spikes from presumed SNpc DAergic cells in vitro, we show that SAF (30 μM) mildly prolongs the DA-mediated firing inhibition, as opposed to the profound effect of TCP (10 μM). In patch-clamp recordings, we found that SAF (30 μM) significantly reduced the number of spikes evoked by depolarizing currents in SNpc DAergic neurons, in a sulpiride (1 μM) independent manner. According to our results, SAF marginally potentiates the DA signal in SNpc DAergic neurons, while exerting an inhibitory effect on the postsynaptic excitability acting on membrane conductances. Thus, we propose that the therapeutic effects of SAF in PD patients partially depends on MAO inhibition, while other MAO-independent sites of action could be more relevant.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Nicola Mercuri reports financial support was provided by Aligning Science Across Parkinson's. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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