(-)-Huperzine A

Short Summary : NMDA receptor antagonist/AChE inhibitor

Category : Neuroscience|Alzheimer

Purity : 0.9999

CAS Number : 102518-79-6

Formula : C15H18N2O

Molecular Weight : 242.3

SMILE : C/C=C1[C@@]2(N)C3=C(NC(C=C3)=O)C[C@]/1([H])C=C(C)C2

Solubility : Limited solubility

Storage : Store at -20°C

Description : ( )-Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor with an IC50 value of 82 nmol/L [1] and acts as an antagonist of the N-methyl-d-aspartate (NMDA) receptor [2].
AChE is the key brain enzyme responsible for the rapid degradation of the neurotransmitter acetylcholine. AChE inhibitors are probably useful in the amelioration of the Alzheimers symptomatology [3].
It was found that NMDA markedly reduced AChE activities [4]. In rat dissociated hippocampal neurons, HupA inhibited the NMDA-induced current. In neurons, 100 M HupA, NMDA-induced currents were 55.7 4.9% of the control values. The binding molecular ratio of NMDA receptor: HupA is 1:1. The inhibition of NMDA receptor by HupA is not competitive [5]. HupA significantly increased the phosphorylation levels of both glycogen synthase kinase (GSK)-3 protein and GSK-3 protein in APPsw-overexpressing cells [2]. Activated GSK-3 consequently decreased acetylcholine (ACh) level in the striatum [6].
Treated with doses of ( )-huperzine A, AChE / mice showed no toxic symptoms and had normal levels of AChE. This demonstrated the specificity of ( )-huperzine A as an inhibitor of AChE at the dose used in vivo [7]. In rat whole brain, oral administration of HupA at a dose of 1.5 mol/kg (3.6 mg/kg) obtained a maximum inhibition of AChE at 60 min and this maximum inhibition was maintained for 360 min [8].
References: [1]. MA Xiao-Chao, XIN Jian, WANG Hai-Xue, et al. Acute effects of huperzine A and tacrine on rat liver. Acta Pharmacol ogica Sinica, 2003, 24(3):247-250.[2]. Zhong Ming Qian and Ya Ke. Huperzine A: is it an effective disease-modifying drug for Alzheimer’s disease Frontiers in Aging Neuroscience, 2014, 6:216.[3]. V. Rajendran, Suo-Bao Rong, Ashima Saxena, et al. Synthesis of a hybrid analog of the acetylcholinesterase inhibitors huperzine A and huperzine B. Tetrahedron Letters, 2001, 42: 5359-5361.[4]. J. R. Delfs, D. M. Saroff, Y. Nishida, et al. Effects of NMDA and its antagonists on ventral horn cholinergic neurons in organotypic roller tube spinal cord cultures. J. Neural Transm., 1997, 104(1):31-51.[5]. J. M. Zhang and G. Y. Hu. Huperzine A, a nootropic alkaloid, inhibits N-methyl-D-aspartate-induced current in rat dissociated hippocampal neurons. Neuroscience, 2001, 105(3):663-9.[6]. L. Zhao, C. B. Chu, J. F. Li, et al. Glycogen synthase kinase-3 reduces acetylcholine level in striatum via disturbing cellular distribution of choline acetyltransferase in cholinergic interneurons in rats. Neuroscience, 2013, 255:203-11.[7]. Ellen G. Duysen, Bin Li, Sultan Darvesh, et al. Sensitivity of butyrylcholinesterase knockout mice to ( )-huperzine A and donepezil suggests humans with butyrylcholinesterase deficiency may not tolerate these Alzheimers disease drugs and indicates butyrylcholinesterase function in neurotransmission. Toxicology, 2007, 233:60-69.[8]. Rui Wang, Han Yan and Xi-can Tang. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacologica Sinica, 2006, 27:1-26.

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