Anticonvulsant Effects of Memantine and MK-801 in Guinea Pig Hippocampal Neurons.
ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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Memantine 1-amino-3,5-dimethyladamantane is used in treatment of Parkinsonism and movement disorders. Recent work has demonstrated that memantine Mem displaces MK-801 from its binding sites, blocks NMDA receptor channels as potently as MK-801, and possesses neuroprotective properties. In this investigation we compared the anticonvulsant properties of Mem to those of MK-801 in guinea pig hippocampal slices. Extracellular recordings were obtained from area CA1 of guinea pig hippocampal slices in a total submersion chamber at 32 deg C in normal oxygenated artificial cerebrospinal fluid ACSF. Evoked responses were elicited by stimulation of Schaffer collateral and commissural fibers. Epileptiform after discharges were induced by bath application of ACSF containing 9-16 uM NMDA or Mg2 -free ACSF continued application of NMDA resulted in suppression of evoked responses. Pretreatment of slices for 15-20 min with 100 uM Mem blocked epileptiform activity induced by both convulsant conditions. At this concentration Mem alone had no discernible effect on evoked responses when perfused for up to 50 min.
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