The effects of memantine (50-175 microM) on the post-tetanic potentiation of the twitch tension were studied on the isolated mouse nerve diaphragm preparation. Memantine completely abolished the twitch tension elicited indirectly while it had no effect on the directly elicited twitch tension. Memantine also decreased the post-tetanic potentiation of amplitude of endplate potential and twitch tension. The duration of tetanic stimulation that induced a maximal decrease of twitch tension was 10-20 s. It is suggested that the effect of memantine on post-tetanic potentiation may be due to its voltage- and time-dependent effect on the ion channel-acetylcholine receptor complex.