(-)-Huperzine A (HupA) 102518-79-6

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Molecular Weight: 242.32 (-)-Huperzine A is a potent, highly specific and reversible inhibitor of acetylcholinesterase (AChE) with Ki of 7 nM, exhibiting 200-fold more selectivity for G4 AChE over G1 AChE. Also acts as an NMDA receptor antagonist. Phase 4.

Biological Activity

(-)-Huperzine A is a novel alkaloid isolated from the Chinese herb
Huperzia serrata. (-)-Huperzine A preferentially inhibits tetrameric
AChE (G4 form). (-)-Huperzine A is more potent than tacrine,
physostigmine, galanthamine, and rivastigmine with respect to inhibition
of AChE activity, whereas HupA is the least potent BuChE inhibitor
among the Inhibitors. (-)-Huperzine A possesses the
ability to protect cells against hydrogen peroxide, β-amyloid protein,
glutamate, ischemia and staurosporine-induced cytotoxicity and
Apoptosis. These protective effects are related to its ability to
attenuate oxidative stress, regulate the expression of apoptotic
Proteins Bcl-2, Bax, P53, and caspase-3, protect mitochondria,
upregulate nerve growth factor and its receptors, and interfere with
amyloid precursor protein Metabolism.






(-)-Huperzine A can ameliorate the learning and memory deficiency in
animal models and AD patients. Its potentially beneficial actions
include modification of β-amyloid peptide processing, reduction of
oxidative stress, neuronal protection against apoptosis, and regulation
of the expression and secretion of nerve growth factor (NGF) and NGF
signaling. (-)-Huperzine A significantly inhibits AChE
activity in the cortex, hippocampus, striatum, medial septum, medulla
oblongata, cerebellum, and hypothalamus of rats that are killed 30 min
following the administration of (-)-Huperzine A at several dose levels
compared with the saline control.





Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×	mouse Km(3)	= 11.2 mg/kg
	rat Km(6)

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