ABSTRACT
Perampanel is an adjunctive treatment for epilepsy that works through the direct inhibition of AMPA receptors. The same molecular mechanism has recently been shown for a fatty acid, decanoic acid, prescribed in the medium chain triglyceride ketogenic diet for the treatment of patients with drug-resistant epilepsy. Because each compound has been proposed to act through a distinct AMPA receptor binding site, we predicted that perampanel and decanoic acid would act synergistically against AMPA receptors and, consequently, seizures. Here, we show a synergistic interaction between perampanel and decanoic acid in direct AMPA receptor inhibition, in an ex vivo model of seizure activity, and against seizure-induced activity in human brain slices. These data support a potential role for combination treatment using perampanel and dietary decanoic acid to provide enhanced seizure control.
Subject(s)
Anticonvulsants/pharmacology , Brain/drug effects , Decanoic Acids/pharmacology , Pyridones/pharmacology , Receptors, AMPA/metabolism , Animals , Dopamine/pharmacology , Dose-Response Relationship, Drug , Drug Synergism , Evoked Potentials/drug effects , Hippocampus/drug effects , Humans , In Vitro Techniques , Nitriles , Oocytes , Pentylenetetrazole/toxicity , Rats , XenopusABSTRACT
The authors report the case of a duplex urinary collecting system that forms a single chamber about 2 cm proximal to the bladder with distal bifurcation and drainage into the bladder via distinct ureteric orifices. This anatomical variant has not been described before.
