Dual Role of 2-Deoxy-D-Glucose in Seizure Modulation

 2-Deoxy-D-glucose (2-DG) is a glucose analog that inhibits glycolysis. Conflicting evidence exists regarding the effects of 2-DG on seizure activity. The effects of 2-deoxy-D-glucose (2-DG) on seizures and epileptogenesis have been a subject of interest in the field of neuroscience and epilepsy research. In the 6-Hz seizure threshold test, 2-DG significantly increased the seizure threshold, indicating anticonvulsant properties. However, in other models, such as the mouse electroshock seizure threshold test, intravenous pentylenetetrazol test, and intravenous kainic acid test, 2-DG decreased the seizure threshold and exhibited proconvulsant effects. Similarly, the related compound 3-methylglucose reduced seizure threshold when administered intravenously with pentylenetetrazol. In contrast, 2-DG administered chronically retarded the progression of kindled seizures in rats, suggesting antiepileptic effects. The anticonvulsant actions of 2-DG may be mediated through the inhibition of glycolysis and diversion of glucose metabolism towards the pentose phosphate pathway. Meanwhile, its acute proconvulsant effects are likely due to reduced glucose uptake. In summary, 2-DG displays both anticonvulsant and proconvulsant actions on seizures, which depend on the model system and mechanisms involved, including glycolytic inhibition and decreased glucose uptake. Further study is needed to fully elucidate the contradictory effects of 2-DG on seizure activity in different experimental models.