Huperzine A
Encyclopedia
Huperzine A is a naturally occurring sesquiterpene alkaloid
compound found in the plant firmoss
Huperzia serrata
. and in varying quantities in other Husperzia spp.including H. elmeri, H. carinat, H. aqualupian,
Huperzine A is also an Acetylcholinesterase inhibitor
, which has a mechanism of action similar to donepezil
, rivastigmine
, and galantamine
. A pro-drug form of Huperzine A (ZT-1) is under development as a treatment for Alzheimer's disease.
In the US, Huperzine A is sold as a dietary supplement for memory support. The botanical has been used in China
for centuries for the treatment of swelling, fever and blood disorders. Clinical trials in China have shown it to be effective in the treatment of Alzheimer's disease and enhancing memory in students.
antagonist.
Huperzine A has also attracted the attention of US medical science. It is currently being investigated as a possible treatment for diseases characterized by neurodegeneration – particularly Alzheimer's disease
. It has been found to be an inhibitor
of the enzyme acetylcholinesterase
. The structure of the complex of huperzine A with acetylcholinesterase has been determined. by X-ray crystallography
(PDB code: 1VOT; see the 3D structure).This is the same mechanism of action
of pharmaceutical drugs such as galantamine
and donepezil
used to treat Alzheimer's disease. Huperzine A is also a NMDA receptor
antagonist
which protects the brain against glutamate induced damage, and it appears to increase nerve growth factor
levels in rats.
Clinical trials in China have shown that huperzine A is comparably effective to similar drugs on the market, and may even be a bit safer in terms of side effects. The National Institute on Aging
has completed a Phase II clinical trial to evaluate the safety and efficacy of huperzine A in the treatment of Alzheimer's disease in a randomized controlled trial
of its effect on cognitive function.The study concluded that huperzine A 200 mug BID has no demonstrable cognitive effect in patients with mild to moderate AD.
Possible side effects include breathing problems, tightness in the throat or chest, chest pain, skin hives, rash, itchy or swollen skin, upset stomach, diarrhea
, vomiting, hyperactivity and insomnia
. Most adverse events were cholinergic in nature and no serious adverse events occurred. Huperzine A is a well-tolerated drug.
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
compound found in the plant firmoss
Firmoss
Huperzia is a genus of Lycophyte plants, sometimes known as the firmosses or fir clubmosses. This genus was originally included in the related genus Lycopodium, from which it differs in having undifferentiated sporangial leaves, and the sporangia not formed into apical cones...
Huperzia serrata
Huperzia serrata
Huperzia serrata is a plant known as a firmoss which contains the acetylcholinesterase inhibitor huperzine A. It is widely distributed over-the-counter as a nootropic and dietary supplement. It may also be used to treat Alzheimer's disease.This species is native to India and southeast Asia.-...
. and in varying quantities in other Husperzia spp.including H. elmeri, H. carinat, H. aqualupian,
Huperzine A is also an Acetylcholinesterase inhibitor
Acetylcholinesterase inhibitor
An acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the cholinesterase enzyme from breaking down acetylcholine, increasing both the level and duration of action of the neurotransmitter acetylcholine.- Uses :Acetylcholinesterase inhibitors:* Occur naturally as...
, which has a mechanism of action similar to donepezil
Donepezil
Donepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the palliative treatment of mild to moderate Alzheimer's disease. Common side effects include...
, rivastigmine
Rivastigmine
Rivastigmine is a parasympathomimetic or cholinergic agent for the treatment of mild to moderate dementia of the Alzheimer’s type and dementia due to Parkinson's disease. The drug can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which...
, and galantamine
Galantamine
Galantamine is used for the treatment of mild to moderate Alzheimer’s disease and various other memory impairments, in particular those of vascular origin...
. A pro-drug form of Huperzine A (ZT-1) is under development as a treatment for Alzheimer's disease.
In the US, Huperzine A is sold as a dietary supplement for memory support. The botanical has been used in China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
for centuries for the treatment of swelling, fever and blood disorders. Clinical trials in China have shown it to be effective in the treatment of Alzheimer's disease and enhancing memory in students.
Pharmacological effects
Huperzine A is an acetylcholinesterase inhibititor and NMDA receptorNMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
antagonist.
Huperzine A has also attracted the attention of US medical science. It is currently being investigated as a possible treatment for diseases characterized by neurodegeneration – particularly Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
. It has been found to be an inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
of the enzyme acetylcholinesterase
Acetylcholinesterase
"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...
. The structure of the complex of huperzine A with acetylcholinesterase has been determined. by X-ray crystallography
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
(PDB code: 1VOT; see the 3D structure).This is the same mechanism of action
Mechanism of action
In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...
of pharmaceutical drugs such as galantamine
Galantamine
Galantamine is used for the treatment of mild to moderate Alzheimer’s disease and various other memory impairments, in particular those of vascular origin...
and donepezil
Donepezil
Donepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the palliative treatment of mild to moderate Alzheimer's disease. Common side effects include...
used to treat Alzheimer's disease. Huperzine A is also a NMDA receptor
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
which protects the brain against glutamate induced damage, and it appears to increase nerve growth factor
Nerve growth factor
Nerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...
levels in rats.
Clinical trials in China have shown that huperzine A is comparably effective to similar drugs on the market, and may even be a bit safer in terms of side effects. The National Institute on Aging
National Institute on Aging
The National Institute on Aging ' is a division of the U.S. National Institutes of Health , located in Baltimore, Maryland.The NIA leads a broad scientific effort to understand the nature of aging and to extend the healthy, active years of life...
has completed a Phase II clinical trial to evaluate the safety and efficacy of huperzine A in the treatment of Alzheimer's disease in a randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
of its effect on cognitive function.The study concluded that huperzine A 200 mug BID has no demonstrable cognitive effect in patients with mild to moderate AD.
Possible side effects include breathing problems, tightness in the throat or chest, chest pain, skin hives, rash, itchy or swollen skin, upset stomach, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, vomiting, hyperactivity and insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
. Most adverse events were cholinergic in nature and no serious adverse events occurred. Huperzine A is a well-tolerated drug.
See also
- Acetylcholinesterase inhibitorAcetylcholinesterase inhibitorAn acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the cholinesterase enzyme from breaking down acetylcholine, increasing both the level and duration of action of the neurotransmitter acetylcholine.- Uses :Acetylcholinesterase inhibitors:* Occur naturally as...
and AChE inhibitors and substrates in ProteopediaProteopediaProteopedia is a wiki, 3D encyclopedia of proteins and other molecules..The site contains a page for every entry in the Protein Data Bank , as well as pages that are more descriptive of protein structures in general such as acetylcholinesterase, hemoglobin, and the photosystem II with a Jmol view...