Biphasic action of dextrorphan on penicillin induced bursting in rat hippocampal slice

Effects of dextrorphan (DX), a metabolite of the over-the-counter antitussive, dextromethorphan, were investigated in rat hippocampal slices exposed to the epileptogenic agent penicillin. At 50 microM and 100 microM concentrations dextrorphan suppressed late components of the epileptiform CA1 field potential elicited by afferent electrical stimulation, and partially suppressed the intracellularly recorded paroxysmal depolarization shift. These effects were not due to non-specific changes in cell excitability, since resting cell membrane potential, input resistance, and the ability of cells to fire action potentials in response to direct depolarizing current were unaffected. The depressant effect of 100 microM dextrorphan was probably due to actions at the NMDA receptor, since pretreatment with the competitive NMDA antagonist D-APV prevented any further depressant effects of dextrorphan in this model. In contrast, at a 10 microM concentration DX enhanced the amplitude of evoked epileptiform field potentials and intracellularly recorded EPSPs. These findings support a role for dextrorphan and similar agents as anticonvulsants at high concentrations, but raise a caution regarding possible excitatory actions of dextrorphan at low concentrations.