Hope for Alzheimer’s Treatment: Cholinesterase Inhibitors
Written by Lillian Brinkmann
Edited by Kelly Chau
July 31st 2021
Edited by Kelly Chau
July 31st 2021
How can we stop Alzheimer’s? A well-known beast, this disease affects 24.3 million people worldwide and impairs vital skills like “decision making, language, memory,” and more. However, a class of drugs called cholinesterase inhibitors can mitigate the effects of the disease. Although they aren’t perfect, scientists continue to research these drugs with the hopes of effectively treating this devastating illness.
Cholinesterase inhibitors increase the presence of an important neurotransmitter called acetylcholine (ACh). According to the cholinergic hypothesis, decreased production of ACh is the primary cause of Alzheimer’s. Furthermore, a type of enzyme known as cholinesterase breaks down the existing acetylcholine. It’s just the body’s way of making sure that there isn’t too much ACh floating around at a given time, but when you don’t have enough to begin with...that esterase becomes a problem.
Cholinesterase (ChE) inhibitors stop this degradation by binding to different parts of the cholinesterase and disrupting its ability to function. This, in turn, allows for a greater concentration of available ACh and diminishes the progression and effects of Alzheimer’s.
There are many types of ChE inhibitors, some of which are commercially available today. Donepezil, Galantamine, and Rivastigmine, for example, are obtainable by prescription though they induce side effects ranging from nausea and stomach pain to low blood pressure and breathing issues. Moreover, these drugs aren’t 100% effective. In search of more successful alternatives, recent studies aim to remedy these issues by identifying other types of cholinesterase inhibitors. One candidate is Phenserine, a ChE inhibitor that has demonstrated improvements in memory and learning in dogs and rats. Through further clinical trials, researchers continue to explore the capabilities of the drug, indicating Phenserine as a promising form of Alzheimer’s treatment.
Naturally derived from plants, other cholinesterase inhibitors under study include Huperzine and Flavonoids. Huperzine originates from the herb Huperzia serrata and can alter the structure of the cholinesterase, rendering it unable to attack ACh. Another Flavonoid, galangin, hails from the ginger plant Alpiniae officinarum and possesses at least a 55% inhibition rate against cholinesterase.
On the flip side, other studies have revolved around entirely man-made compounds. Synthetically creating ChE inhibitors enables us to tailor them more closely in order to avoid nasty effects like stomach pains and liver damage. Such compounds, like Ladostigil and Indenyl derivatives, have exhibited moderate success. For example, one study found that the chemical makeup of Ladostigil allowed the drug to more effectively target cholinesterase.
As a final type of ChE inhibitor, mixtures of drugs like donepezil-tacrine and donepezil-AP2238 aim to combine the strength of the individual components. The two compounds in Donepezil-tacrine work together by simultaneously attacking the esterase, demonstrating that they function better together than they do alone.
As researchers continue to explore different compounds through clinical trials and studies, cholinesterase inhibitors serve as promising candidates for the future of Alzheimer’s treatment. Whether these chemical guardians come from plants, straight from the lab, or somewhere in between, it’s safe to say that our acetylcholine is in good hands.
Image Source: “3d medical figure with brain highlighted” by Kirsty Pargeter licensed under Freepik License