Memantine reduces repetitive action potential firing in spinal cord nerve cell cultures

(1) The anticonvulsant effects of memantine were examined and compared with those of baclofen in monolayer primary cultures of murine nerve cells using conventional intracellular recordings. (2) Memantine and baclofen (each 10-100 microM) decreased spontaneous synaptic activity when action potential frequencies exceeded 6 Hz. Neurons firing action potentials at frequencies below 6 Hz (about 90% of all impaled cells), however, were not affected by the drugs. (3) Memantine reduced the duration of strychnine-elicited bursts and the firing rate of action potentials within a burst. In contrast, baclofen lowered the frequency of the bursts without reducing intra-burst firing. The duration of the bursts was increased. (4) Memantine, but not baclofen, reduced the extent of sustained repetitive firing evoked by pulses of depolarizing current. (5) In the presence of memantine, the second of two electrically evoked action potentials increasingly failed to appear as the intervals between successive stimulating pulses were shortened. Such an effect was not seen when baclofen was applied. Thus, both antispastic agents, memantine and baclofen, reduce hyperactivity of spinal cord neurons in culture, although their mechanisms of action are different.