To assess the effects of cholinesterase inhibitors huperzine A, donepezil and rivastigmine on cerebral neurotransmitters in the cortex and hippocampus in freely-moving rats.
Double-probe cerebral microdialysis and HPLC with electrochemical detection were used to detect neurotransmitters.
Our results showed that huperzine A (0.25, 0.5, and 0.75 μmol/kg, po) dose-dependently elevated extracellular acetylcholine (ACh) levels in the medial prefrontal cortex (mPFC) and hippocampus. Oral administration of donepezil (5.4 μmol/kg) or rivastigmine (1 μmol/kg) also elicited significant increases in ACh in the mPFC and hippocampus. The time course of cortical acetylcholinesterase (AChE) inhibition with the 3 inhibitors mirrored the increases of ACh at the same dose. The marked elevation of ACh after oral administration of huperzine A (0.5 μmol/kg) and donepezil (5.4 μmol/kg) was associated with a significantly increased release of dopamine (DA) in the mPFC or hippocampus. None of the 3 inhibitors affected norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels in the mPFC and hippocampus. The effects of huperzine A and rivastigmine did not depend on the route of administration, but donepezil was less efficacious by the oral route than by ip injection. The ability of huperzine A to increase ACh levels was unchanged when tests were performed after multiple oral administration of the drug at 0.5 μmol/kg, once per day for 30 d.
The present findings showed that, in molar terms, huperzine A had similar potency on increasing mPFC ACh and DA levels as compared to the 11- and 2-fold dosages of donepezil and rivastigmine, respectively, and had longer lasting effects after oral dosing.
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Project supported by the National Natural Science Foundation of China (No 30123005).
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Liang, Yq., Tang, Xc. Comparative studies of huperzine A, donepezil, and rivastigmine on brain acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine levels in freely-moving rats. Acta Pharmacol Sin 27, 1127–1136 (2006). https://doi.org/10.1111/j.1745-7254.2006.00411.x
- huperzine A
- 5-hydroxy tryptamine
- Alzheimer's disease