NMDA Receptor Antagonists
Examples
Memantine
Indications
Memantine is currently prescribed to patients with moderate or severe Alzheimer's Disease.
Contraindications
Contraindications
- Like with Acetylcholinesterase Inhibitors, breast feeding is an absolute contraindication to taking Memantine.
Caution
- History of convulsions
- Renal Impairment (as Memantine is excreted via the kidneys)
Mechanism
At normal levels, the neurotransmitter glutamate is involved in many beneficial processes, including learning and memory. However, when levels of glutamate become too high, it can over stimulate neurones, causing a process known as "Neuronal Excitotoxicity." This occurs when neurones are killed by excessive stimulation from neurotransmitters such as glutamate. In simple terms, receptors are overreacted and this causes an influx of calcium ions into the neurone. This influx of calcium activates a number of enzymes which then cause damage to cell structures such as the cytoskeleton, cell membrane, and cell DNA.
One type of receptor which can be affected by neuronal excitotoxicity is NMDA (N-Methyl-D-aspartate) receptors. NMDA Receptor Antagonists block the NMDA Receptor from glutamate and therefore, in theory, prevent the entire process of neuronal excitotoxicity.
The rationale for using this class of drug in Alzheimer's Disease is that it prevents the neuronal death which leads to the symptoms experienced by patients.
Administration
Memantine hydrochloride is taken as oral tablets or oral drops.
Adverse Reactions
Memantine is generally quite well tolerated amongst patients, but side effects do include:
- Constipation
- Hypertension
- Headache
- Dizziness
- Drowsiness
Rare side effects include:
- Vomiting
- Thrombosis
- Heart Failure
- Confusion
- Hallucinations
- Fatigue
Extremely rare side effects include:
- Seizures
- Pancreatitis
- Psychosis
- Depression
Interactions
As memantine is excreted via the kidneys, drugs which are also eliminated via the kidneys can interact with it. For example cimetidine, hydrochlorothiazide, nicotine, quinidine and ranitidine must all be used with caution in conjunction with memantine.
Other NMDA Antagonists such as Methadone, Tramadol and Ketamine must be used with caution when a patient is on Memantine.
Education
As with Acetylcholinesterase Inhibitors, patients must be realistic about the benefits of NMDA Receptor Antagonists. Although they may help relieve symptoms, they are not a "cure" of Alzheimer's Disease, and do not necessarily halt the disease process.
It is important to note that Memantine should be reserved for moderate or severe in Alzheimer's Disease, and recent research has supported the previous hypothesis that it has no role in milder forms of the disease.
Pharmacokinetics
Memantine is not metabolised by the hepatic system, and is eliminated via the kidneys.
