The novel antiepileptic drug lacosamide blocks behavioral and brain metabolic manifestations of seizure activity in the 6 Hz psychomotor seizure model.
Brain metabolic activation after 6 Hz electrical stimulation (32 mA, 3s stimulus duration) was assessed by autoradiographic analysis of 14C-2-deoxyglucose (2-DG) uptake. In addition, effects of the new antiepileptic drug lacosamide were examined on the stimulation-induced metabolic activation. The 6 Hz stimulation via corneal electrodes induced a robust increase 2-DG uptake in cerebral cortical regions, lateral amygdala, and the caudate-putamen. Many other brain regions were not affected by the stimulation, including the hippocampal formation, medial nuclei of the amygdala, thalamus, and hypothalamus. Lacosamide (20 mg/kg) injected i.p. 30 min before application of electrical stimulation antagonized completely the seizure-induced brain metabolic activation but did not affect basal 2-DG uptake. The data provide evidence that lacosamide antagonizes the neural activation induced by an electrical seizure stimulus, without suppressing normal brain metabolic activity.
Duncan
Gary E
GE
Department of Psychiatry, School of Medicine, CB# 7090, 410 Taylor Hall, University of North Carolina, Chapel Hill, NC 27599-7090, USA. gduncan@med.unc.edu
Kohn
Harold
H
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004558:Electric Stimulation; D017029:Epilepsy, Complex Partial / Q000188:drug therapy*; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D000078334:Lacosamide; D051379:Mice
D000081:Acetamides; D000927:Anticonvulsants; D002250:Carbon Radioisotopes; D000078334:Lacosamide; D003847:Deoxyglucose; D005947:Glucose