Pharmacology of Huperzine A Potent selective AChE inhibitor which caused a significant increase in ACh levels (0.1, 0.3 and 0.5 mg/kg by 54%, 129% and 220%, respectively in animal models). Selective for brain AChE over peripheral AChE (reducing peripheral cholinergic side effects). Has a long duration of actions, high bioavailability after oral administration, and has stronger or equivalent inhibition over AChE when compared with current prescribed inhibitor. Huperzine had positive effect for symptoms of depression, delusions and repetitive activities in AD. Potent multifaceted neuroprotective effects Regulating β-amyloid precursor protein metabolism, protecting against β-amyloid-mediated oxidative stress and apoptosis. NMDA antagonist activity NGF promoting activity Effects on mitochondria Significant dose-dependent increase over baseline of brain norepinephrine (NE) and dopamine (DA) in the cortex (more than 100% after the 0.3 and 0.5 mg/kg doses) In non-clinical populations it increased the scores of ‘‘accumulation,’’ ‘‘recognition,’’ ‘‘association,’’ ‘‘factual memory’’ and ‘‘number of recitations,’’ but not ‘‘understanding,’’ a result the authors found consistent with the findings from learning performance References A. Zangara, The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer’s disease Pharmacology, Biochemistry and Behavior 75 (2003) 675–686 doi:10.1016/S0091-3057(03)00111-4 1 Tuo Ma, Kai Gong, Yufang Yan, Lihai Zhang, Peifu Tang, Xiufang Zhang, Yandao Gong, Huperzine A promotes hippocampal neurogenesis in vitro and in vivo, Brain Research, Volume 1506, 2013, Pages 35-43, doi:10.1016/j.brainres.2013.02.026. J.-M Zhang, G.-Y Hu, Huperzine A, a nootropic alkaloid, inhibits N-methyl-D-aspartate- induced current in rat dissociated hippocampal neurons, Neuroscience, Volume 105, Issue 3, 2001, Pages 663-669, doi:10.1016/S0306-4522(01)00206-8. Zhang, H.Y., Yan, H. & Tang, X.C. Non-cholinergic Effects of Huperzine A: Beyond Inhibition of Acetylcholinesterase. Cell Mol Neurobiol 28, 173–183 (2008). doi:10.1007/s10571-007-9163-z 2