D-cycloserine, a putative cognitive enhancer, facilitates activation of the N-methyl-D-aspartate receptor-ionophore complex in Alzheimer brain.
The action of D-Cycloserine (DCS) at the strychnine-insensitive glycine recognition site of the NMDA receptor-ionophore complex has been studied with membranes from inferior parietal cortex of patients with Alzheimer's disease. The maximal response of the site, measured using [3H]MK-801 binding, was 64% of that observed with glycine. Stimulation of binding induced by DCS in the presence of fixed concentrations of glycine resulted in a family of dose-response curves, consistent with the antibiotic having the property of a partial agonist at this glycine site. It is proposed that because of circumscribed glutamatergic pyramidal cell pathology DCS will have benefit for Alzheimer's patients over and above all other types of cognitive impairment.
Chessell
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Miriam Marks Department of Neurochemistry, Institute of Neurology, London, U.K.
Procter
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Francis
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Bowen
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D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects*; D003523:Cycloserine / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D007476:Ionophores / Q000737:chemistry; D011869:Radioligand Assay; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000187:drug effects*; D013237:Stereoisomerism
D007476:Ionophores; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D003523:Cycloserine