Features of psychological reactions induced by perampanel: A case report

Yamada, Shoko M.; Tomita, Yusuke; Takaya, Yoshinori

doi:10.1111/jcpt.13141

Cited by 3 publications

(1 citation statement)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is increasing amount of clinical research revealing that the long-term use of perampanel for refractory partial-onset epilepsy has caused an abundance of concern about the adverse events and health risks of aggressive behavior. − However, the underlying pathogenesis and neurobiological significance remain poorly understood. In our current study, we have carried out quantitative proteomic methods to identify changes in protein profile alternations induced by PER in the hippocampus of an aggressive behavior mice model.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal Proteomic Analysis in Male Mice Following Aggressive Behavior Induced by Long-Term Administration of Perampanel

Yang

Hai

et al. 2022

ACS Omega

View full text Add to dashboard Cite

Antiepileptic drugs have been shown to be associated with inducing or exacerbating adverse psychotropic reaction, including aggressive behavior. Perampanel, the first pharmacological compound approved by the FDA in 2012, is an effective antiepileptic drug for intractable epilepsy but induces severe aggression. So far, the underlying molecular mechanisms of aggression induced by perampanel remain incompletely understood. In the present study, a model of aggressive behavior based on the clinical use of perampanel was established and resident–intruder test and open field test were performed. Changes in hippocampal protein profiles were detected by tandem mass tag (TMT) proteomics. The behavioral results indicated that long-term use of perampanel increased the aggressive behavior of C57BL/6J mice. Proteomic analysis revealed that 93 proteins were significantly altered in the hippocampus of the perampanel-treated group (corrected p < 0.05), which were divided into multiple functional groups, mainly related to synaptic function, synaptogenesis, postsynaptic density protein, neurite outgrowth, AMPA-type glutamate receptor immobilization, and others. Bioinformatic analysis showed that differentially expressed proteins were involved in synaptic plasticity and the Ras signaling pathway. Furthermore, validation results by western blot demonstrated that glutamate receptor 1 (GluA1) and phosphorylation of mitogen-activated protein kinase (ERK1/2) were notably up-regulated, and synaptophysin ( Syn ) and postsynaptic density 95 (PSD95) were down-regulated in perampanel-treated mice. Therefore, our results provide valuable insight into the molecular mechanisms of aggressive behavior induced by perampanel, as well as potential options for safety treatment of perampanel in the future.

show abstract

Section: Discussionmentioning

confidence: 99%