Most medicines for Alzheimer’s disease improve your symptoms rather than treat the disease itself. A type of drug that’s often prescribed soon after you’re diagnosed is called a cholinesterase inhibitor. While these drugs don’t change the course of your disease, they may help with thinking and memory problems.
Cells in your brain called neurons make a chemical called acetylcholine that helps brain cells communicate with each other. It has a role in many cognitive functions, including:
- Attention
- Learning
- Memory
- Information processing
It’s also involved in regulating your sleep and helping you respond to stress.
Alzheimer’s disease destroys the neurons that make acetylcholine. Over time, you have less than you need. The acetylcholine you do have is gradually broken down as it gets used. Cholinesterase inhibitors slow this process. That makes more of the chemical available to your brain for as long as possible.
Acetylcholinesterase inhibitors
Cholinesterase inhibitors have other names, including anticholinesterase and acetylcholinesterase (AChE) inhibitors.
Cholinesterase Inhibitor Drugs
The FDA has approved three cholinesterase inhibitors for Alzheimer’s treatment.
Donepezil (Aricept)
Donepezil treats mild, moderate, and severe Alzheimer’s disease.
- You take it once a day either as a tablet you swallow or one that dissolves in your mouth.
- Side effects include fatigue, muscle cramps, nausea, vomiting, loss of appetite, and diarrhea.
Donepezil plus memantine (Namzaric)
Donepezil plus memantine combines a cholinesterase inhibitor with a different Alzheimer’s medication called an NMDA agonist. The NMDA agonist controls levels of a different brain chemical called glutamate. The combination is approved to treat moderate to severe Alzheimer’s.
- You take this once a day as a tablet you swallow.
- Donepezil plus memantine side effects can include headache, confusion, dizziness, constipation, nausea, vomiting, loss of appetite, and diarrhea.
Galantamine (Razadyne)
Galantamine is used to treat mild-to-moderate Alzheimer’s disease.
- You take this either twice a day as a tablet you swallow, or once a day as an extended-release capsule.
- Galantamine side effects include headaches, dizziness, nausea, vomiting, loss of appetite, and diarrhea.
Rivastigimine (Exelon)
Rivastigmine is used for mild to moderate Alzheimer’s disease. In patch form, it’s approved for severe Alzheimer’s.
- You take this twice a day as a capsule you swallow. It also comes as a patch you stick to your skin and change daily.
- Rivastigmine side effects include muscle weakness, indigestion, nausea, vomiting, loss of appetite, and diarrhea. You may have fewer digestive side effects if you use the patch instead of the pill.
If you have side effects when you start taking a cholinesterase inhibitor, they may go away as you get used to the medicine. Your doctor may be able to give you tips to help you manage them, like taking your medication with meals.
Your doctor will probably start you on a low dose and increase it if the side effects don’t bother you. Not everyone responds to every one of these drugs, and they may not work for you at all. You may need to try more than one to find what’s right for you.
Other Types of Cholinesterase Inhibitors
Researchers have explored other types of cholinesterase inhibitors for treatment of Alzheimer’s in the past. They include:
Tacrine
Tacrine was the first drug the FDA approved for treating Alzheimer’s. Doctors used to prescribe it for mild to moderate Alzheimer’s.
- You take tacrine as a pill by mouth four times a day.
- Typically, side effects include diarrhea, nausea, vomiting, stomach pain, dizziness, headache, anxiety, blurred vision, dry mouth, and insomnia.
As newer cholinesterase inhibitors with fewer side effects became available, the manufacturer withdrew it from the market in 2013.
Physostigmine (Eserine)
Researchers began studying the cholinesterase drug physostigmine (eserine) in the 1980s as a drug to improve memory in people with and without dementia. In the early 2000s, marketers tried several versions of the drug to try to prevent side effects, such as a controlled-release pill and a patch.
Side effects included diarrhea, stomach cramps, excessive sweating, and increased saliva. Because the benefits of the drugs didn’t outweigh these side effects, the FDA did not approve it for the treatment of Alzheimer’s.
Metrifonate
This anticholinesterase drug was originally prescribed for treating a condition called schistosomiasis, which is an infection from a parasite. When researchers tested it for memory improvement in people with Alzheimer’s, some people in the clinical trials had trouble with the muscles they used for breathing.
As a result, the manufacturer recalled their application to the FDA. This drug isn’t available in the U.S.
How Well Do Cholinesterase Inhibitors Work?
Research found that many who take cholinesterase inhibitors have modest improvement of their symptoms that can last for several years. You may find you’re able to think more clearly, learn and remember things better, and manage your daily activities more easily. There doesn’t appear to be a difference in how well these drugs work based on your age, gender, or ethnicity.
But the effects of cholinesterase inhibitors are temporary. The drugs don’t stop or fix the damage that Alzheimer’s does to your brain. Eventually, your brain stops making enough acetylcholine for cholinesterase inhibitors to help anymore.
Who Shouldn’t Take Cholinesterase Inhibitors?
Cholinesterase inhibitors can lower your heart rate and blood pressure. If you already have an unusually slow heartbeat or you take high blood pressure medication, they can make you likely to faint and fall. They might not be a good choice for you if you have:
- Asthma
- Certain abnormal heart rhythms (or heartbeats)
- Kidney disease
- Liver disease
- Ulcers
To avoid dangerous interactions, make sure your doctor knows about all medicines and supplements you take.
You should not take a kind of drug called an anticholinergic while you’re taking a cholinesterase inhibitor. Anticholinergics are prescribed for things like depression, psychosis, and bladder problems. They’re also in some over-the-counter cold medicines and sleep aids. The drugs work opposite of each other and combining them can make both work poorly.
Takeaways
Cholinesterase inhibitors (acetylcholinesterase inhibitors) are drugs that can prevent the breakdown of acetylcholine so that more is available to nerve cells in the brain. Acetylcholine is a chemical messenger that helps your brain cells communicate with each other. The three most common cholinesterase inhibitors are donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon).
Cholinesterase Inhibitors FAQs
What is the function of cholinesterase?
Cholinesterase is an enzyme that helps your nervous system work the way it should. It breaks down acetylcholine, which is a chemical messenger in your brain so you don’t get overstimulated.
What is the first drug of choice for Alzheimer’s?
The Alzheimer’s drug that works best for you will depend on many factors including the stage of your Alzheimer’s disease. Most people with Alzheimer’s will take either cholinesterase inhibitors, memantine, or brexpiprazole.
