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.
Lampe
H
H
Department of Pharmacology and Toxicology, Medical School of Hannover, Germany.
Bigalke
H
H
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018118:Chloride Channels; D005333:Fetus; D005998:Glycine / Q000494:pharmacology*; D007473:Ion Channels / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018118:Chloride Channels; D007473:Ion Channels; D008565:Membrane Proteins; D005680:gamma-Aminobutyric Acid; D000547:Amantadine; D000218:Adamantane; D005998:Glycine