Do. Norris et al., A GLYCINERGIC INTERVENTION POTENTIATES THE ANTISEIZURE EFFICACIES OF MK-801, FLURAZEPAM, AND CARBAMAZEPINE, Neurochemical research, 19(2), 1994, pp. 161-165
Twenty four hours after mice were forced to swim for up to 10 minutes
in cold water, there was a reduction in the ability of MK-801 to antag
onize the electrical precipitation of tonic hindlimb extension, Milace
mide, a lipophilic prodrug of glycine, restored the antiseizure effica
cy of MK-801 to the same level observed in unstressed animals treated
with milacemide and MK-801. Stimulation of the glycine-gated chloride
ionophore subsequent to the liberation of free glycine could explain m
ilacemide's pharmacologic action as an adjuvant to MK-801. Consistent
with this interpretation, milacemide was able to potentiate the antise
izure effects of flurazepam, a benzodiazepine agonist, in stressed and
unstressed mice and carbamazepine in unstressed animals. D-cycloserin
e, a partial glycine agonist with greater specificity for the strychni
ne-insensitive modulatory site on the NMDA receptor complex, was exami
ned for its effect on MK-801's antiseizure efficacy. At a high dose (3
20 mg/kg), D-cycloserine alone had an anticonvulsant effect. Moreover,
this dose of D-cycloserine administered with MK-801 showed a signific
antly greater anticonvulsant efficacy than MK-801 alone. The data supp
ort the development of glycinergic interventions as adjunctive agents
in the pharmacotherapy of seizure disorders.