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Effect of huperzine A, a new cholinesterase inhibitor, on the central cholinergic system of the rat.

Journal of neuroscience research (1989-10-01)
X C Tang, P De Sarno, K Sugaya, E Giacobini

The present study represents the first comprehensive investigation of the effect of huperzine A (HUP-A), a new cholinesterase inhibitor (ChEI) isolated from a Lycopodium species, upon acetylcholinesterase (AChE) activity, acetylcholine (ACh) levels and release, and cholinergic receptors in rat brain following acute i.m. or i.p. administration. The study shows that HUP-A can produce a long-term inhibition of AChE activity in brain (up to 360 min) and an increase in the ACh levels up to 40% at 60 min. There is considerable regional variation in the degree of ACh elevation after HUP-A with maximal values seen in frontal (125%) and parietal (105%) cortex and smaller increases (22-65%) in other brain regions. HUP-A at concentrations of 10(-6) to 10(-4) M does not significantly alter the electrically evoked release of 3H-ACh from cortical slices. With the exception of the highest concentrations (6 X 10(-4) M) the displacement effect of HUP-A for cholinergic ligands is stronger for 3H-(-)nicotine than for 3H-QNB. A parallel autoradiographic study in the mouse shows that 60 min after i.v. injection (183 micrograms/kg) the drug is present in all brain regions, but it is particularly concentrated in certain areas such as frontoparietal cortex, nucleus accumbens, hippocampal, and striatal cortex. Radio-activity is practically absent in the whole body at 12 hr. Our study suggests that this new ChEI has interesting cholinomimetic properties, and its effects satisfy more closely established criteria for an ideal ChEI for therapeutic use than previously tested compounds.

Product Number
Product Description

(±)-Huperzine A, synthetic, ≥98% (TLC)

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