Modafinil alleviates levodopa-induced excessive nighttime sleepiness and restores monoaminergic systems in a nocturnal animal model of Parkinson's disease

• Published in: Journal of pharmacological sciences 2018-04, Vol.136 (4), p.266-271
• Main Authors: Ando, Rina, Choudhury, Mohammed Emamussalehin, Yamanishi, Yuki, Kyaw, Win Thiri, Kubo, Madoka, Kannou, Mariko, Nishikawa, Noriko, Tanaka, Junya, Nomoto, Masahiro, Nagai, Masahiro
• Format: Article
• Language: English
• Subjects: Animals; Antiparkinson Agents - administration & dosage; Antiparkinson Agents - pharmacology; Antiparkinson Agents - therapeutic use; Arousal - drug effects; Benzhydryl Compounds - administration & dosage; Benzhydryl Compounds - pharmacology; Benzhydryl Compounds - therapeutic use; Biogenic Monoamines - metabolism; Disease Models, Animal; Disorders of Excessive Somnolence - chemically induced; Disorders of Excessive Somnolence - drug therapy; Drug Therapy, Combination; Excessive day time sleepiness; Levodopa - administration & dosage; Levodopa - adverse effects; Male; Mice, Inbred C57BL; Modafinil; Monoamines; MPTP; Neurorestoration; Nocturnal; Parkinson Disease - drug therapy; Parkinson's disease; Photoperiod
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2018.03.005

Treatment with dopaminergic agents result excessive daytime sleepiness (EDS) and some studies have shown the benefit of using modafinil for treating excessive daytime sleepiness of Parkinson's disease (PD) patient. We investigated whether modafinil have ameliorative properties against levodopa induced excessive nighttime sleepiness (ENS) in MPTP-treated murine nocturnal PD model. Our EEG analyses of whole day recordings revealed that modafinil reduce ENS of this nocturnal PD models with levodopa medications. Therefore, we investigated whether, modafinil post-treatment followed by MPTP shows any effect on monoamine contents of brain and found to robustly increased noradrenaline (NA) concentration of MPTP treated mice. Modafinil post-treatment, in neurorestorative context (5 days post-lesion) led to increased striatal dopamine (DA) concentrations of MPTP-treated mice. Here, we first confirmed that modafinil ameliorates levodopa induced excessive sleepiness and restores monoaminergic systems. The arousal and anti-parkinsonian effects displayed by modafinil indicate that in combination with dopaminergic agents, modafinil co-administration may be worthwhile in trying to suppress the excessive daytime sleepiness and progressive dopaminergic neuron loss in PD.