Abstract
The inhibition of huperzine A, a potential therapeutic agent to treat Alzheimer's disease, on rat cortical acetylcholinesterase was found to be highly stereospecific. In the present study the effect of the enantiomers of huperzine A on [(3)H]dizocilpine (MK-801) binding to synaptic membrane of rat cerebral cortex was compared. The natural (-)-huperzine A and the synthetic (+)-huperzine A inhibited the specific binding of [(3)H]MK-801 with a similar potency. The IC(50) values were 65+/-7 and 82+/-12 microM (n=5 for each enantiomer, P=0.248), respectively. The result indicates that huperzine A inhibits N-methyl-D-aspartate (NMDA) receptor in rat cerebral cortex without stereoselectivity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids
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Alzheimer Disease / drug therapy
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Alzheimer Disease / metabolism
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Animals
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Binding Sites / drug effects*
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Binding Sites / physiology
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Cerebral Cortex / cytology
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Cerebral Cortex / drug effects*
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Cerebral Cortex / metabolism
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Cholinesterase Inhibitors / pharmacology
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Dizocilpine Maleate / pharmacokinetics*
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Drug Interactions / physiology
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism
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Neuroprotective Agents / chemistry
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Neuroprotective Agents / pharmacology*
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Radioligand Assay
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Rats
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Receptors, N-Methyl-D-Aspartate / drug effects*
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Receptors, N-Methyl-D-Aspartate / metabolism
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Sesquiterpenes / chemistry
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Sesquiterpenes / pharmacology*
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Stereoisomerism
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Synaptic Membranes / drug effects*
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Synaptic Membranes / metabolism
Substances
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Alkaloids
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Cholinesterase Inhibitors
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Neuroprotective Agents
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Receptors, N-Methyl-D-Aspartate
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Sesquiterpenes
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huperzine A
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Dizocilpine Maleate