Huperzine A

Huperzine A (HupA; CAS 102518-79-6; molecular formula C15H18N2O; molecular weight 242.32) is a sesquiterpene alkaloid extracted from the Chinese club moss Huperzia serrata, identified in the 1980s by researchers at the Shanghai Institute of Materia Medica. The compound is a selective reversible acetylcholinesterase inhibitor (Ki approximately 20 nM, comparable potency to donepezil) with substantially better blood-brain barrier penetration than the synthetic AChE inhibitors used clinically (donepezil, rivastigmine, galantamine). A secondary mechanism is NMDA receptor antagonism at low affinity, providing partial neuroprotection against glutamatergic excitotoxicity. Huperzine A is approved as a drug in China for vascular dementia and Alzheimer disease and is sold as a dietary supplement in the United States and Europe. Pharmacokinetics include plasma half-life of approximately 4 to 5 hours and good oral bioavailability. Clinical evidence base in Alzheimer disease and mild cognitive impairment includes multiple Chinese-language and several English-language randomized trials with modest effect sizes on cognitive endpoint measures. Reported research dose ranges in the literature span 50 to 200 micrograms; the compound is potent and the dose range is correspondingly low. Safety considerations include cholinergic adverse events at higher doses (nausea, diaphoresis, bradycardia); the upper end of the reported research range is established by tolerability rather than dose-response saturation.