Effects of alkyl-substituted gamma-butyrolactones and succinimides on the evoked and spontaneous activity of hippocampal slices in vitro.

Alkyl-substituted and unsubstituted derivatives of gamma-butyrolactone (GBL), gamma-hydroxybutyrate (GHB), and succinimide were tested for their effects on the evoked potential (EP) and spontaneous activity of hippocampal slices incubated in vitro. When tested alone, only beta-ethyl-beta-methyl-GBL (beta-EMGBL) and tetramethylsuccinimide (TMSM) had any effect, producing greatly augmented EPs and spontaneous epileptiform discharges. The nonexcitatory drugs were also tested for the ability to block the excitation produced by beta-EMGBL, TMSM, and penicillin. The unsubstituted compounds had no effect on the augmented EP induced by any of the convulsants. The alpha-ethyl-alpha-methyl-substituted GBL (alpha-EMGBL) and ethosuximide (ESM), blocked the augmented EP induced by beta-EMGBL and TMSM but not that induced by penicillin. The spontaneous activity induced by all three excitatory agents was blocked by GHB. Unsubstituted succinimide had no effect on spontaneous activity. The spontaneous activity produced by beta-EMGBL and TMSM was blocked by alpha-EMGBL, but ESM blocked only that induced by TMSM. Neither alpha-EMGBL nor ESM blocked the spontaneous activity produced by penicillin. We conclude that the ability to block the EP more closely parallels in vivo anticonvulsant activity whereas effects on the spontaneous activity may be more related to neuronal depressant effects. The alkyl-substituted GBLs and succinimides had very similar, albeit not identical, effects on incubated hippocampal slices. That may indicate that they have a similar but not a common mechanism of action.