Memantine inhibits [3H]MK-801 binding to human hippocampal NMDA receptors
1994; Lippincott Williams & Wilkins; Volume: 5; Issue: 10 Linguagem: Inglês
10.1097/00001756-199406020-00020
ISSN1473-558X
AutoresWolfgang Berger, Jürgen Deckert, Joachim Hartmann, Christine Krotzer, Johannes Kornhuber, Gerhard Ransmayr, H. Heinsen, H. Beckmann, Peter Riederer,
Tópico(s)Epilepsy research and treatment
ResumoThe antispastic agent andN-methyl-D-aspartate (NMDA) receptor antagonist memantine has recently been proposed as a neuroprotective drug for use in patients with dementia syndromes with primarily temporal lobe pathology, e.g. senile dementia of Alzheimer type or dementia in Parkinson's disease. In a quantitative autoradiographic study in human post mortem hippocampus, memantine was able to inhibit binding of the noncompetitive NMDA-antagonist [3H]MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate) with inhibition constants between 3 and 10 μM, being about a factor of 10 more potent than the dissociative anaesthetic and NMDA receptor antagonist (±)ketamine. As these inhibition constants are well within the therapeutic concentration range of memantine, antagonism of endogenous glutamate at limbic NMDA receptors may be one molecular mechanism by which memantine is beneficial in dementia syndromes.
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