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

• Published in: Neuroscience letters 2000-12, Vol.295 (3), p.116-118
• Main Authors: Zhang, Yun-Hai, Chen, Xue-Qin, Yang, Hui-Hua, Jin, Guang-Yi, Bai, Dong-Lu, Hu, Guo-Yuan
• Format: Article
• Language: English
• Subjects: [ 3H]dizocilpine (MK-801) binding; Alkaloids; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease; Animals; Binding Sites - drug effects; Binding Sites - physiology; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cholinesterase inhibitor; Cholinesterase Inhibitors - pharmacology; Dizocilpine Maleate - pharmacokinetics; Drug Interactions - physiology; Enantiomers; Fundamental and applied biological sciences. Psychology; Huperzine A; N-methyl- d-aspartate receptor; 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; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(00)01615-3

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 [ 3H]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 [ 3H]MK-801 with a similar potency. The IC 50 values were 65±7 and 82±12 μM ( 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.