The ability of nerve cells to communicate with each other is mainly achieved by neurotransmitters. Acetylcholine (Ach) is an extremely important neurotransmitter in the brain. When its content in the brain is high, the nerve conduction function of the memory brain area is relatively strong, the information transmission speed between the cranial nerves is fast, the human memory is strong, and various brain functions are improved accordingly. On the contrary, if its amount is reduced, the nerve conduction function of the memory brain area will be weakened, the information transmission speed between the cranial nerves will be slow, and the human memory will decline, and various brain dysfunctions will occur, such as Alzheimer's disease. However, in the synaptic cleft of nerve cells, Ach released from the presynaptic membrane transmits nerve impulses and is soon hydrolyzed by acetylcholinesterase (AchE).
★Mechanism
Huperzine A can increase the half-life of Ach. A depression in the three-dimensional structure of acetylcholinesterase (AchE) is its active site. Both Ach and Hup A can enter, but Huperzine A is hydrolyzed slowly after entering. The AchE activity is inhibited, resulting in the accumulation of Huperzine A released from cholinergic nerve endings, resulting in a cholinergic effect.
★Inhibition strength
Huperzine A can increase the level of acetylcholine in the cerebral cortex of rats, and this effect is stronger and longer than that of donepezil and esner, and the increase of acetylcholine level can last at least 6h after administration. The effect of Huperzine A on increasing the level of acetylcholine varies with different brain regions: the frontal cortex and parietal cortex have the most obvious increase at 60 minutes after administration, while the hippocampus and medulla have moderate increases at 30 minutes and 5 minutes after administration, respectively. , the striatum was only slightly elevated 30 min after administration. Since Huperzine A can selectively distribute in the cortex, hippocampus and other brain regions related to learning and memory in the central nervous system, it can obviously promote memory, memory process or significantly improve memory impairment. Due to the low level of acetylcholine in the cerebral cortex of AD patients, Huperzine A has a selective effect on cortical regions, so it is beneficial to the treatment of AD.
★High selectivity
Experiments on the inhibition of acetylcholinesterase activity in rat cerebral cortex in vitro showed that Huperzine A had a stronger inhibitory effect on acetylcholinesterase activity than tacrine, galantamine and esner, and was slightly weaker than donepezil, but had a stronger inhibitory effect on serum acetylcholinesterase activity. The concentration required for butyrylcholinesterase inhibition was much higher than that of donepezil, tacrine, esner and galantamine, indicating that Huperzine A has obvious selective inhibitory effect on acetylcholinesterase. The inhibition of acetylcholinesterase by intraperitoneal injection or intragastric administration of Huperzine A to rats is similar, indicating that Huperzine A has better oral bioavailability and is more likely to penetrate the blood-cerebrospinal fluid barrier. There was no significant difference in the inhibitory effect of Huperzine A for multiple administrations or single administration, indicating that Huperzine A does not develop drug resistance when repeated administration.
Huperzine A has a strong inhibitory effect on acetylcholinesterase G4 isoforms in different brain regions, which is very different from tacrine, donepezil, physostigmine and esner. The most abundant subtype in most brain regions of mammals is the G4 subtype. The extracellular G4 subtype is the most important acetylcholinesterase that regulates the content of acetylcholine in the brain. The specificity of Huperzine A to the G4 subtype acetylcholinesterase The inhibitory effect is more beneficial to the treatment of AD.
If you want to know more, please consult medical@ysgcn.com
