Development of huperzine A and B for treatment of Alzheimer's disease

Acetylcholinesterase (AChE) remains a highly viable target for the symptomatic improvement in Alzheimer's disease (AD) because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AchE for myasthenia gravis had effectively proven that AchE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEI) continue to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs in development and their respective mechanisms of actions. This pharmacological approach continues to be active with many promising compounds.

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“…It is also in Phase II clinical trials in Europe [16]. Phase II trials have also been conducted in over 30 sites in the US.…”

Section: Naturally Derivedmentioning

confidence: 99%

New Acetylcholinesterase Inhibitors for Alzheimer's Disease

Mehta

Adem

Sabbagh

2012

International Journal of Alzheimer's Disease

326

272

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“…The genus Lycopodium (Lycopodiaceae), which produces a potential therapeutic agent, huperzine A, for the treatment of AD, has been extensively studied in recent years [66]. Huperzine A is an alkaloid extracted from Lycopodium serratum and has been used for centuries to treat fever, inflammation, blood disorders and schizophrenia [67]. It is a highly selective, reversible, and potent AChE inhibitor, and potency of AChE inhibition is similar or superior to that of physostigmine, galanthamine, donepezil and tacrine [68].…”

Section: Lycopodium Serratummentioning

confidence: 99%

Herbal Medicines as Neuroprotective Agent: A Mechanistic Approach

Roy

Awasthi

2017

Int J Pharm Pharm Sci

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Neurodegeneration refers to a condition of neuronal death occurring as a result of progressive disease of long-term and is becoming a major health problem in the 21st century. Neurons degenerated are not replaced resulting in a cognitive loss, many neurodegenerative disorders, such as schizophrenia, depression, Alzheimer's disease (AD), dementia, cerebrovascular impairment, seizure disorders, head injury, parkinsonism. The common pathology of neurodegeneration includes deposition of misfolded proteins such as amyloid-β (Aβ) in Alzheimer's disease, α-synuclein in Parkinson's disease (PD), transactive response DNA-binding protein 43 (TDP-43) in dementia. Neuroprotection refers to the strategies and possible mechanisms that are able to protect the central nervous system (CNS) against neuronal injury and neurodegenerative disorders. The past decade has witnessed an intense interest in herbal plants having long-term health-promoting or medicinal qualities. Comprehensive research and discovery have demonstrated that natural products, medicinal herbs, plant extracts, and their metabolites, have great potential as the neuroprotective agent. Although the precise mechanisms of action of herbal drugs have yet to be determined, some of them have been shown to prevent formation of betaamyloid plaques, promote nerve growth, some inhibit acetylcholinesterase (AChE) enzyme and malondialdehyde (MDA) formation in brain while other exhibits antioxidant activity by increasing the level of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). Thus the herbal plants can be a valuable source of the drug against neurodegenerative disorders which will require high-throughput screening. This review will highlight the role of herbal plants and their phytoconstituents against neurodegenerative diseases and other related disorders, focusing on their mechanism of action and therapeutic potential.

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“…123,124 ). Huperzine A is a more potent AChE inhibitor than huperzine B. Huperzine can be isolated from the H. serrata that contains above 0.025 (w/w) of huperzine A and less huperzine B; synthetic production is available as well 125 . Donepezil is another drug suitable for Alzheimer's disease treatment with good penetration through the blood brain barrier and slow excretion.…”

Section: Inhibitors Of Peripheral (β) Anionic Sitementioning

confidence: 99%

Cholinesterases, a Target of Pharmacology and Toxicology

Pohanka¹

2011

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

325

219

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Background. Cholinesterases are a group of serine hydrolases that split the neurotransmitter acetylcholine (ACh) and terminate its action. Of the two types, butyrylcholinesterase and acetylcholinesterase (AChE), AChE plays the key role in ending cholinergic neurotransmission. Cholinesterase inhibitors are substances, either natural or man-made that interfere with the break-down of ACh and prolong its action. Hence their relevance to toxicology and pharmacology.Methods and Results. The present review summarizes current knowledge of the cholinesterases and their inhibition. Particular attention is paid to the toxicology and pharmacology of cholinesterase-related inhibitors such as nerve agents (e.g. sarin, soman, tabun, VX), pesticides (e.g. paraoxon, parathion, malathion, malaoxon, carbofuran), selected plants and fungal secondary metabolites (e.g. aflatoxins), drugs for Alzheimer's disease (e.g. huperzine, metrifonate, tacrine, donepezil) and Myasthenia gravis (e.g. pyridostigmine) treatment and other compounds (propidium, ethidium, decamethonium).Conclusions. The crucial role of the cholinesterases in neural transmission makes them a primary target of a large number of cholinesterase-inhibiting drugs and toxins. In pharmacology, this has relevance to the treatment of neurodegenerative disorders.

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Development of huperzine A and B for treatment of Alzheimer's disease

Cited by 51 publications

References 54 publications

New Acetylcholinesterase Inhibitors for Alzheimer's Disease

New Acetylcholinesterase Inhibitors for Alzheimer's Disease

Herbal Medicines as Neuroprotective Agent: A Mechanistic Approach

Cholinesterases, a Target of Pharmacology and Toxicology

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