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  • Title: Second generation cholinesterase inhibitors: effect of (L)-huperzine-A on cortical biogenic amines.
    Author: Zhu XD, Giacobini E.
    Journal: J Neurosci Res; 1995 Aug 15; 41(6):828-35. PubMed ID: 7500384.
    Abstract:
    L-Huperzine-A (Hup-A), a natural cholinesterase inhibitor (ChEI) derived from the Chinese herb Huperzia serrata, was administered systemically (i.p.) or locally through the microdialysis probe into the rat cortex. Systemic Hup-A significantly increased acetylcholine (ACh) levels above baseline at doses of 0.1, 0.3, and 0.5 mg/kg; the increases were 54%, 129%, and 220%, respectively. Norepinephrine (NE) and dopamine (DA) levels were also increased 121% and 129% above baseline at 0.3 mg/kg, and 143% and 153% at 0.5 mg/kg. Peak cholinesterase (ChE) inhibition was 23% at 60 min with the 0.3 mg/kg dose. Huperzine-A, perfused through the microdialysis probe, produced a maximal increase of ACh levels of 3090% and 7790% at concentrations of 5 and 50 microM. The ACh increase seen at both concentrations lasted at least 6 hr. At the 5-microM dose, NE and DA were increased by 214% and 386%; at the 50-microM dose, NE and DA were increased by 216% and 1141%. There were no changes of 5-HT levels. With local administration (via the probe), both doses produced facial-forelimb seizures that lasted throughout the perfusion. Our results show that Hup-A is a potent inhibitor of ChE which penetrates into the brain and produces a dose-dependent increase of ACh, NE, and DA in rat cortex. This effect is seen with both systemic and local intracerebral administration, suggesting cortical as well as subcortical effects of the drug.
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