Is an AChE inhibitor the drug molecule itself as a whole or it is contained in a drug molecule? Please assist
I don't know if this responde to you, anyway: there are three main achE inhibitors, one are the reversible, they bind in the catalitic pocket by reversible interactions such as hydrogen bonds or saline bonds, like
Ambenonium which have two ammonium salt similarly to the coline portion of achetilcoline. Then you have the reversible but with slow regeneration of the active site, like neostigmine. this substance has an urethane on the moleucle which is able to do a covalent bond to the serine in the activev site. The urethane formed with the resine can be hydrolized by water but slower than that with acetetyl ester comeing by acetilcoline hydrolisys. Finally we have the irreversible inhibitors. They are molecules such as organophosfates, or poinsoning gas like sarin. They ar eable to made a organophosfate ester at the catalitic serine, which is stable, may be reverted by the use of pralidoxime, but the complex will evolve fast to aging, by loosing ethanol residue, and then the enzyme cannot be regenerated.
Dear Dr. Mollica,
Yes that covers my question well and more.
Thank you for your reply.
There are two types of AChE inhibitors: reversible and irreversible acetylcholinesterase inactivating compounds.
Irreversible AChE inhibitors are organophosphorus compounds such as insecticides and nerve agents that were originally developed in the 1940s as highly toxic biological warfare agents.
Reversible AChE inhibitors are anticholinesterases medicines, such as donepezil, rivastigmine and galantamine (for Alzheimer’s disease); or neostigmine, pyridostigmine and distigmine (for myasthenia gravis).
The term “AChE inhibitors” is related to both, irreversible and reversible AChE inhibitors, while the term “AChE inhibitors drugs” is related only to reversible AChE inhibitors i.e. to antihlinesterases drugs.
Please read the following publications:
1. Colovic et al 2013, related to pharmacology and toxicology of AChE inhibitors, using the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648782/pdf/CN-11-315.pdf
2. Mehndiratta et al, 2014, related to acetylcholinesterase inhibitor treatment for myasthenia gravis, using the following link:
http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD006986.pub3/epdf
Hello.
The etiology of Alzheimer's disease is multifarious so are the hypothesis related to it. AChE inhibitors are modeled on the cholinergic hypothesis of AD. They work by inhibiting the activity of enzyme AChE which is responsible for the breakdown of Acetylcholine, a neurotransmitter whose levels decline in AD. Currently there are two types of drugs for AD.
One is the class of AChE inhibitors, which are actually reversible. The second is memantine which works through another mechanism of blockade of current flow through channels of N-methyl-d-aspartate (NMDA) receptors--a glutamate receptor subfamily broadly involved in brain function. Reversible AChE inhibitors would traditionally work as a drug in the purview of AD.
However to be considered a drug, there comes many additional factors like lipophilicity parameter, topological parameter as well as quantification of any possible toxicity. Merely acting as an AChE inhibitor does not automatically indicate that the compound could be administered as a drug.
Thank you colleagues for your insightful replies/answers to my question. They have really been helpful.
Kind regards
https://www.drugdevelopment-technology.com/projects/phenserine/
more information
Thank you Dr. Ahmad
I have gone through it and Phenserine promises some cutting edge interventions.
Thank you for the link. Given me a better understnding
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