Similar potency of the enantiomers of huperzine A in inhibition of [(3)H]dizocilpine (MK-801) binding in rat cerebral cortex

Neurosci Lett. 2000 Dec 8;295(3):116-8. doi: 10.1016/s0304-3940(00)01615-3.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Animals
  • Binding Sites / drug effects*
  • Binding Sites / physiology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Cholinesterase Inhibitors / pharmacology
  • Dizocilpine Maleate / pharmacokinetics*
  • Drug Interactions / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Radioligand Assay
  • Rats
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Stereoisomerism
  • Synaptic Membranes / drug effects*
  • Synaptic Membranes / metabolism

Substances

  • Alkaloids
  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Receptors, N-Methyl-D-Aspartate
  • Sesquiterpenes
  • huperzine A
  • Dizocilpine Maleate