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Treatments & Cholinesterase Inhibitors - DementiaGuide.com
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Treatments for Dementia

Cholinesterase Inhibitors

Acetyl Choline | Donepezil | Rivastigmine | Galantamine

There is one class of drugs now in use which is the mainstay for the treatment of Alzheimer's disease . The cholinesterase [ko-lin-S-ter-aze] inhibitors now include three drugs in routine use. Their action can be a little complicated to understand, but it sometimes helps to think of the old story of "the house that Jack built": this is the stick that hit the dog that barked at the cat that chased the mouse that lived in the house that Jack built. Similarly, a cholinesterase inhibitor can be thought of as the drug that inhibits the enzyme that breaks down the chemical that is important for memory . The drugs (there are three - donepezil, rivastigmine and galantamine) act by inhibiting the protein (an enzyme, called cholinesterase) that breaks down the chemical (called acetyl choline) that is important for memory. By inhibiting the breakdown, the allow more of the memory chemical (acetyl choline) to be present.

Cholinesterase inhibitors work to increase the amount of acetyl choline in the brain, where they increase memory performance. They also increase acetyl choline outside the brain, and this can give rise to side effects. The stomach, intestines and bowels are also places where acetyl choline acts, so an upset stomach and diarrhea are common side effects of these drugs. Similarly, acetyl choline regulates the heart rate, so another side effect can be slowing of the heart rate, which can sometimes cause fainting, although this is not common. Any drug can give rise to nausea , rash, or severe allergic reactions, and these drugs are not exception, although the last problem is rare. Also, any drug can interact with other drugs, and that too needs to be kept in mind by the physician who prescribes any of these medications.

In general, however, the cholinesterase inhibitors have been well studied, and over a large number of clinical trials they have been found to work, on average. Specifically, it has been shown that the drugs have worked across clinical trials and that higher doses do better than lower ones. The key here is that the studies show that the drugs work on average: a group of people who take the drugs does better than a group of people who take a placebo (an inactive substance, also known as a "sugar pill"). What has been controversial, however, is how well they work in individual patients. By allowing people to track specific symptoms, the SymptomGuideTM can help people understand whether a particular treatment is helping.

Acetyl choline

The brain is made up of billions of neurons. Neurons communicate with each other by making links across the miniscule gaps between them. These gaps are called synapses. Communication across the gap occurs by the release of brain chemicals from the transmitting neuron to the receiving neuron. These brain chemicals are called neurotransmitters.

There are many different types of neurotransmitters within neurons. The first neurotransmitter to be discovered was acetyl choline. Neurons containing acetyl choline are known as cholinergic neurons. Acetyl choline is involved in sending many types of messages throughout the brain, including those involving memory and learning. Acetyl choline is made up of two parts, acetyl-CoA and choline, which both may be found in our diet. Acetyl-CoA comes from the regular fats and sugars in our diet. Choline forms from lecithin , which is found in animal and plant-based foods like eggs, liver, peanuts or soybeans. Acetyl-CoA and choline are joined together in the neuron by a type of protein called an enzyme, forming acetyl choline. This neurotransmitter travels to the end of axon where it is released into the synapse. Acetyl choline carries a chemical message which is recognized by special sites on the next neuron. The message is sent until another enzyme enters the synapse to break down acetyl choline. This enzyme is called acetylcholinesterase . At this point the message stops until the process begins again.


In Alzheimer's disease, the amount of acetyl choline is diminished. The original strategy to replace acetyl choline was simply to add items like lecithin to the diet. This strategy proved to be ineffective for a number of reasons. Also unsuccessful was supplying more acetyl choline, or drugs that functioned like acetyl choline. Finally, the best approach was to inhibit the brain enzyme that breaks down acetyl choline. That enzyme is called acetylcholinesterase, and thus the drugs that inhibit it are called cholinesterase inhibitors.


AriceptTM is the trade name for donepezil. It is a cholinesterase inhibitor, making it a drug from the main class of compounds now used to treat people with Alzheimer's disease. AriceptTM has been used in a large number of clinical trials, including some from Canada that have used a variety of individualized symptom-based tests of its effectiveness.

On October 13th, 2006, the US Food and Drug Administration approved AriceptTM as a treatment for severe dementia associated with Alzheimer's disease. With its approval a decade ago for mild-to-moderate Alzheimer's dementia, AriceptTM becomes the first sanctioned drug to treat all forms of the memory- robbing disease, the FDA said in a statement. The latest approval followed clinical testing in Sweden and Japan.

Briefly, it is taken once a day, with food. The starting dose is 5 mg/day. After a month on the drug, if it is well tolerated, most patients will be increased to the 10 mg/day dose. Usually, at least two months more are needed to know whether the drug is meeting the goals of treatment.


ExelonTM and Exelon TMPatch are the trade names for rivastigmine. It is a cholinesterase inhibitor for the treatment of Alzheimer's disease. It is also used to treat people with Lewy body dementia, and with the dementia of Parkinson's disease .

The starting dose is 1.5 mg, twice a day. Typically, after one month, this is increased to 3.0 mg, twice a day, which is often the lowest effective dose. Patients who tolerate that dose can have it increased to a dose of 4.5 mg twice a day, and later to a dose of 6.0 mg twice a day. These are the recommended doses. Individual patients might find that their doctors will recommend other doses, depending on their tolerability, and the drug's effects in their cases.

Exelon TMPatch is now available in some countries, including the United States and Canada. It is applied to the back, chest or upper arm and provides continuous delivery of medication through the skin over 24 hours. Treatment is initiated with Exelon TMPatch 5 (9mg/5cm2) with a release rate of 4.6mg over a 24 hour period to a maximum dosage of Exelon TMPatch 10 ( 18mg/10cm2) with a release rate of 9.5mg over a 24 hour period.


Reminyl ER is the trade name for galantamine in Canada, Reminyl XL in the UK, and in the United States, the trade name for galantamine is Razadyne (and the extended release formulation is called Razadyne ER). It is a cholinesterase inhibitor, making it a drug from the main class of compounds now used to treat people with Alzheimer's disease. Reminyl has been used in a large number of clinical trials, including an important, placebo-controlled trial from Canada which used an individualized symptom-based test to evaluate its effectiveness. (This report on galantamine is available for free online). The reference to the paper is Rockwood K, et al., Attainment of treatment goals by people with Alzheimer's disease receiving galantamine: a randomized controlled trial, CMAJ 2006 174: 1099-1105. In addition to acting like the other cholinesterase inhibitors, it also directly stimulates a class of receptors to which acetyl choline binds. Whether this offers a precise advantage over other cholinesterase inhibitors is not clear, but what is clear is that not all drugs work equally well for all people, so having different drugs with different mechanisms of action offers people choice.

Briefly, galantamine (extended release) is taken once a day, with food. The starting dose is 8 mg/day. After a month on the drug, if it is well tolerated, most patients will be increased to the 16 mg/day dose, and there is also a 24 mg/day dose. Usually, at least two months after starting at the 16 mg/day dose are needed to know whether the drug is meeting the goals of treatment.

See Also:
About Dementia > Alzheimer's Disease > Cholinergic Theory
About Dementia > Alzheimer's Disease > Memory
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Last updated January 15, 2019
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