Seizure suppression via glycolysis inhibition with 2-deoxy-D-glucose (2DG).
Metabolic regulation of neuronal excitability is increasingly recognized as a factor in seizure pathogenesis and control. Inhibiting or bypassing glycolysis may be one way through which the ketogenic diet provides an anticonvulsant effect. 2-deoxy-D-glucose (2DG), a nonmetabolizable glucose analog that partially inhibits glycolysis, was tested in several acute and chronic seizure models. Acutely, 2DG decreases the frequency of high-K(+)-, bicuculline- and 4-aminopyridine-induced interictal bursts in the CA3 region of hippocampal slices; 2DG also exerts anticonvulsant effects in vivo against perforant path kindling in rats. Chronically, 2DG has novel antiepileptic effects by retarding the progression of kindled seizures. Finally, 2DG has a favorable preliminary toxicity profile. These factors support the possibility that 2DG or other modifiers of glycolysis can be used as novel treatments for epilepsy.
Stafstrom
Carl E
CE
Department of Neurology, University of Wisconsin, Madison, Wisconsin 53792, USA. stafstrom@neurology.wisc.edu
Roopra
Avtar
A
Sutula
Thomas P
TP
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects*; D006801:Humans; D007696:Kindling, Neurologic / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D012640:Seizures / Q000188:drug therapy*
D000927:Anticonvulsants; D003847:Deoxyglucose