Details

Autor(en) / Beteiligte

• Pisanò, Clarissa A.
• Brugnoli, Alberto
• Novello, Salvatore
• Caccia, Carla
• Keywood, Charlotte
• Melloni, Elsa
• Vailati, Silvia
• Padoani, Gloria
• Morari, Michele

Titel

Safinamide inhibits in vivo glutamate release in a rat model of Parkinson's disease

Ist Teil von

• Neuropharmacology, 2020-05, Vol.167, p.108006, Article 108006

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• To investigate whether the reversible MAO-B inhibitor and sodium channel blocker safinamide impairs glutamate release under parkinsonian conditions in vivo, and this effect is dependent on MAO-B inhibition, safinamide (and rasagiline as a comparator) were administered to 6-hydroxydopamine hemilesioned rats, a model of Parkinson's disease, and haloperidol-treated rats, a model of neuroleptic-induced parkinsonism. A microdialysis probe was implanted in the dopamine-depleted dorsolateral striatum, globus pallidus, subthalamic nucleus or substantia nigra reticulata of 6-hydroxydopamine hemilesioned rats. Glutamate and GABA release was stimulated by reverse dialysis of veratridine, and safinamide or rasagiline were acutely administered before veratridine at doses inhibiting MAO-B >50%. A microdialysis probe was implanted in the substantia nigra reticulata of naïve rats to monitor glutamate and GABA release following acute haloperidol and safinamide administration. Safinamide inhibited the veratridine-evoked glutamate release in the globus pallidus and subthalamic nucleus but not in the striatum and substantia nigra. Moreover, it reduced pallidal and nigral GABA release. Conversely, rasagiline failed to modify the veratridine-induced glutamate and GABA release in the basal ganglia. Safinamide also inhibited the haloperidol-induced nigral glutamate release. MAO-B inhibitors safinamide and rasagiline differ in their abilities to inhibit depolarization-evoked glutamate release in the basal ganglia of parkinsonian rats. The ineffectiveness of rasagiline suggests that MAO-B inhibition does not contribute to the antiglutamatergic activity of safinamide. The glutamate-inhibiting action of safinamide within the subthalamo-external pallidal loop, which shows abnormal activity in Parkinson's disease, might contribute to its therapeutic actions of improving motor performance without provoking troublesome dyskinesia. •Safinamide inhibits in vivo glutamate release in GP and STN of 6-OHDA rats.•Rasagiline does not affect glutamate release in 6-OHDA rats.•Safinamide inhibits in vivo glutamate release in SNr of haloperidol-treated rats.•The glutamate-inhibiting action of safinamide in MAO-B independent.