Modulation of glycine-activated membrane current by adamantane derivatives

Pressure application of the inhibitory neurotransmitters glycine and GABA, respectively, evoked a Cl- current in spinal cord neurons of fetal mice in culture. Memantine, in low concentrations (0.3-5 microM) enhanced the glycine-mediated current at both negative and positive holding potentials. At concentrations of more than 5 microM, memantine increased the glycine-evoked current only when the membrane potential was positive. At negative potentials the current was inhibited. 3-isopropylamantadine and 3,5-diethylamantadine augmented the glycine-activated membrane current irrespective of the concentrations applied, whereas amantadine was ineffective. The GABA-activated Cl- current was not altered by the adamantanes. These data are evidence of a specific glycinergic interaction with putative antispastic agents and can explain some conflicting effects of memantine in experimentally induced seizures.