Anticonvulsant and proconvulsant actions of 2-deoxy-D-glucose.
OBJECTIVE
2-Deoxy-D-glucose (2-DG), a glucose analog that accumulates in cells and interferes with carbohydrate metabolism by inhibiting glycolytic enzymes, has anticonvulsant actions. Recognizing that severe glucose deprivation can induce seizures, we sought to determine whether acute treatment with 2-DG can promote seizure susceptibility by assessing its effects on seizure threshold. For comparison, we studied 3-methyl-glucose (3-MG), which like 2-DG accumulates in cells and reduces glucose uptake, but does not inhibit glycolysis.


METHODS
Mice were treated with 2-DG or 3-MG and the seizure threshold determined in the 6-Hz test, the mouse electroshock seizure threshold (MEST) test, and the intravenous pentylenetetrazol (i.v. PTZ) or kainic acid (i.v. KA) seizure threshold tests. 2-DG was also tested in fully amygdala-kindled rats.


RESULTS
2-DG (125-500 mg/kg, i.p., 30 min before testing) significantly elevated the seizure threshold in the 6-Hz seizure test. 2-DG (250-500 mg/kg) decreased the threshold in the MEST and i.v. PTZ and i.v. KA tests. 3-MG had no effect on seizure threshold in the 6-Hz test but, like 2-DG, decreased seizure threshold in the i.v. PTZ test. 2-DG (250 and 500 mg/kg, i.p., 30 min before testing) had no effect on amygdala-kindled seizures.


CONCLUSIONS
Although 2-DG protects against seizures in the 6-Hz seizure test, it promotes seizures in some other models. The proconvulsant action may relate to reduced glucose uptake, whereas the anticonvulsant action may require inhibition of glycolysis and shunting of glucose metabolism through the pentose phosphate pathway.
Gasior
Maciej
M
Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Yankura
Jessica
J
Hartman
Adam L
AL
French
Amy
A
Rogawski
Michael A
MA
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D000963:Antimetabolites / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D007608:Kainic Acid / Q000009:adverse effects; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D051379:Mice; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology; D010433:Pentylenetetrazole / Q000009:adverse effects; D051381:Rats; D012640:Seizures / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors
D000927:Anticonvulsants; D000963:Antimetabolites; D001786:Blood Glucose; D003847:Deoxyglucose; D007608:Kainic Acid; D020155:3-Hydroxybutyric Acid; D010433:Pentylenetetrazole