Perampanel is a novel drug recently approved as adjunctive therapy in epileptic patients aged 12 years and older who have drug-resistant partial epilepsy with and without secondary generalization. Pharmacological researches revealed that perampanel reduces neuronal excitability by a non-competitive antagonistic activity against the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors causing modulation of glutamatergic neurotransmission. The pharmacological profile of the drug showed complete absorption following oral administration, and extensive metabolism in the liver by oxidation followed by glucuronidation with an elimination half-life of approximately 53-165 h (average: 105 h), allowing once-daily administration. Randomized placebo-controlled trials demonstrated an effective dose range of the drug, between 4 and 12 mg/day, to significantly reduce seizure frequency in patients with partial-onset seizure that are pharmacoresistant with a favorable tolerability profile. The most frequent adverse events of the drug reported in phase III clinical trials were dizziness, somnolence, fatigue, and headache. However, the data raised from the studies can give a hope that perampanel offers a valuable option as an adjuvant therapy for pharmacoresistant partial-onset and secondarily generalized seizures.
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http://dx.doi.org/10.1111/fcp.12081 | DOI Listing |
PLoS Biol
January 2025
Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Medical University, Fuzhou, China.
The anterior cingulate cortex (ACC) is recognized as a pivotal cortical region involved in the perception of pain. The retrosplenial cortex (RSC), located posterior to the ACC, is known to play a significant role in navigation and memory processes. Although the projections from the RSC to the ACC have been found, the specifics of the synaptic connections and the functional implications of the RSC-ACC projections remain less understood.
View Article and Find Full Text PDFJ Physiol
January 2025
Université Paris Cité, CNRS, Saints-Pères Paris Institute for the Neurosciences, Paris, France.
Fañanas cells (FCs) are cerebellar glia of unknown function. First described more than a century ago, they have been almost absent from the scientific literature ever since. Here, we combined whole-cell, patch clamp recordings, near-UV laser photolysis, dye-loading and confocal imaging for a first characterization of FCs in terms of their morphology, electrophysiology and glutamate-evoked currents.
View Article and Find Full Text PDFBehav Brain Res
January 2025
Laboratorio de Neurobiología, División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica (IPICYT), San Luis Potosí, Mexico. Electronic address:
Ketamine hydrochloride serves multiple purposes, including its use as a general anesthetic, treatment for depression, and recreational drug. In studies involving rodents, ketamine is utilized as a model for schizophrenia. However, it is unclear whether age affects the behavioral response induced by repeated ketamine administration and if it modifies the expression levels of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and purinergic receptors (P2X1, P2X4, P2X7).
View Article and Find Full Text PDFCell Mol Neurobiol
January 2025
Laboratory of Neurobiology, Centro de Investigaciones Medico Sanitarias (CIMES), University of Malaga, Calle Marqués de Beccaria, 3, Campus Teatinos s/n, 29010, Malaga, Spain.
Tetrameric AMPA-type ionotropic glutamate receptors are primary transducers of fast excitatory synaptic transmission in the central nervous system, and their properties and abundance at the synaptic surface are crucial determinants of synaptic efficacy in neuronal communication across the brain. The induction of long-term potentiation (LTP) leads to the insertion of GluA1-containing AMPA receptors at the synaptic surface, whereas during long-term depression (LTD), these receptors are internalized into the cytoplasm of the spine. Disruptions in the trafficking of AMPA receptors to and from the synaptic surface attenuate both forms of synaptic plasticity.
View Article and Find Full Text PDFInt J Neurosci
January 2025
Department of Mathematics, Payame Noor University, Tehran, Iran.
The developing brain undergoes a remarkable process of synapse production and maturation, particularly in glutamatergic synapses. In this study, we focused on the locus coeruleus (LC) nucleus, a brain region crucial for cognitive functions, to investigate the developmental changes in glutamatergic synaptic connections. Using the whole-cell patch clamp method, we recorded evoked excitatory postsynaptic currents (eEPSCs) from LC neurons in rats at ages 7, 14, and 21 days.
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