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.
Keywords: Anticonvulsant, Epilepsy, Proconvulsant, Seizure, Synaptic excitation, Seizure threshold, 2-Deoxy-D-glucose.
