Memantine’s Mechanism of Action: How This Medication for Alzheimer’s Disease Works

Alzheimer’s disease (AD) is the most common form of dementia. Dementia is a general term for conditions that cause a decline in brain functions. For example, dementia may affect your problem-solving skills and ability to remember things.

Memantine (Namenda) is a prescription medication that treats moderate to severe dementia related to AD. In this article, we’ll review memantine’s mechanism of action. We’ll also cover a few other facts, including how long it takes to work.

What is memantine?

Memantine is prescribed to treat moderate to severe dementia associated with AD. It’s also sometimes prescribed for AD in earlier stages. Memantine comes as an immediate-release tablet and oral liquid and an extended-release capsule.

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Memantine is often used with other medications, called cholinesterase inhibitors, to treat AD. Examples include donepezil (Aricept, Adlarity) and rivastigmine (Exelon). A combination of memantine and cholinesterase inhibitors may work better to improve AD symptoms than either medication alone, especially for moderate to severe AD. In fact, a combination capsule containing donepezil and memantine is available (Namzaric).

Keep in mind that memantine and cholinesterase inhibitors don’t treat the cause of AD. This means they don’t prevent AD from progressing. But they can improve symptoms of dementia. This includes worsening memory, attention span, and language abilities.

Newer medications can slow down the progression of AD. More on this later.

What is memantine’s mechanism of action?

Memantine blocks the effects of a neurotransmitter in the body called glutamate. Neurotransmitters are chemical messengers that help the brain and nervous system communicate.

Glutamate is the body’s primary excitatory neurotransmitter. It’s involved in several brain functions, such as memory and learning. But when glutamate is too active, it may contribute to the development of AD.

Memantine decreases glutamate activity by binding to sites in the brain and body. These sites are called N-methyl-D-aspartate (NMDA) receptors. When memantine binds to NMDA receptors, glutamate can’t attach, making it less active. This helps improve some AD symptoms, such as problems with memory and attention.

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When does memantine start working?

Most studies on memantine are designed to determine whether memantine improves AD symptoms within 3 to 6 months. But compared with placebo (a medication with nothing in it), some research shows that memantine can start to improve AD symptoms within a month.

Keep in mind that it may take several weeks for your prescriber to find the most effective dose for you. Memantine is started at a lower dose to give your body time to get used to the medication. This also lowers the risk of side effects.

How do you know if memantine is working?

Memantine may improve your ability to function. It can help you perform daily tasks more easily and may improve your memory. But memantine isn’t a cure for AD. AD is a progressive condition. This means brain function is likely to continue to decline, even if you take memantine. That decline may be slower with medication.

Studies of memantine use a few tools to determine how well it’s working. Examples include:

• The Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale. This survey helps gauge your ability to independently complete tasks. Examples include eating, bathing, and dressing. It’s meant to be completed by a caregiver or a healthcare professional. Lower scores indicate greater trouble with tasks of daily living.

• The Severe Impairment Battery (SIB) test. The SIB can help assess how well memantine is working. It evaluates attention, memory, language, and more. It is administered by a healthcare professional. Lower scores represent greater cognitive impairment.

Your prescriber may administer these or other tests before and after you start memantine. This will help them determine if your AD symptoms are improving. Additionally, tracking your symptoms at home can help. For example, keep a symptom journal. This is a useful tool for noticing symptom improvement with memantine.

Are there alternatives to memantine for dementia?

Besides memantine, several other medications treat AD. Medications are divided into three broad groups:

• Medications that target symptoms of dementia (but don’t treat the underlying cause of AD)

• Cholinesterase inhibitors, such as donepezil, galantamine, and rivastigmine

• NMDA receptor antagonists, such as memantine

• Medications that target the underlying pathways in the body that cause AD

  • Anti-amyloid medications, such as Leqembi (lecanemab) and Kisunla (donanemab)

• Medications that target other symptoms of AD (such as trouble sleeping and agitation)

• Rexulti (brexpiprazole) for agitation related to dementia

• Belsomra (suvorexant) for insomnia related to Alzheimer’s

Your prescriber may recommend combining two or more of these medications to treat AD.

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Written by:

Alex Brewer, PharmD, MBA

Alex Brewer, PharmD, MBA, is a licensed pharmacist specializing in chronic disease and health and wellness. Upon completing his residency, he worked in the managed care field, conducting medication therapy management and adherence counseling sessions with Medicaid, Medicare, and private insurance patients, before transitioning to a career in medical writing.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Patricia Pinto-Garcia, MD, MPH

Patricia Pinto-Garcia, MD, MPH, is a medical editor at GoodRx. She is a licensed, board-certified pediatrician with more than a decade of experience in academic medicine.

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