2-Deoxyglucose

Metabolic regulation of excitability is increasingly appreciated as a strategy to control seizures and reduce pathogenesis. Inhibiting or bypassing glycolysis may be one way in which the ketogenic diet suppresses seizures. 2-deoxy-D-glucose (2DG) is a glucose analog that partially inhibits glycolysis and has antiseizure effects in several acute and chronic seizure models. The mechanisms underlying the acute and chronic effects of 2DG are being investigated. Preliminary studies provide evidence that the acute anticonvulsant actions of 2DG involve activity-dependent presynaptic suppression of excitatory synaptic transmission during network synchronization. The chronic effects of 2DG entail reduction of the expression of brain-derived neurotrophic factor and its receptor, tyrosine kinase B. Preclinical toxicology studies demonstrate that 2DG has a favorable toxicity profile at doses effective for seizure protection. Currently available preclinical studies support 2DG as a novel first-in-class metabolic treatment for epilepsy with an antiglycolytic mechanism distinct from all other anticonvulsants.