How Alzheimer’s Disease Drugs Work

By American Geriatrics Society (AGS)

The four medicines used to treat Alzheimer’s disease (AD) divide into two groups according to the different ways in which they work: Acetylcholinesterase inhibitors — Donepezil, rivastigmine, galantamine; NMDA receptor antagonist — Memantine (a very small and lonely group of one!).

Here’s a quick guide to their different mechanisms of action.

Acetylcholinesterase inhibitors

Scientists have found that in AD, the most common form of dementia, patients lose nerve cells in the brain that communicate with each other using a chemical neurotransmitter called acetylcholine. As a result, communication is blocked, and messages can’t easily flow from one part of the brain to another. That means the person can’t form new memories or recall them, and will develop other cognitive, behavioral, and functional changes that are characteristic of AD.

The drugs in this group work by blocking the effect of an enzyme (enzymes are proteins in the body that promote chemical reactions) called acetylcholinesterase that breaks down acetylcholine. Acetylcholinesterase inhibitors therefore boost the level of acetylcholine, allowing the brain cells to communicate better.

Memantine

Glutamate is one of the brain’s main activating chemical neurotransmitters involved in the processes underlying learning and memory. Researchers believe that the overexcitation of the NMDA (short for N methyl D aspartate) receptors by too much glutamate causes too much stimulation in brain cells, which causes their dysfunction and eventual cell death that occurs in the brain of AD patients.

Memantine is an NMDA receptor antagonist, meaning that it binds to the NMDA receptors on brain cells thereby stopping too much glutamate from attaching to these receptors and triggering this damaging chain of events. The important thing is that memantine still lets the proper amount of glutamate attach to the NMDA receptors on the brain cells, allowing more normal brain cell function. This, in turn, helps protect the brain cells from excess stimulation and thereby slows the progression of the damage seen in AD.