Memantine

Molecular mechanism of action

From a pharmacodynamic perspective, memantine acts as a non-competitive, low-affinity NMDA receptor antagonist. Under physiological conditions, the ion channel of this receptor is blocked by magnesium ions ($Mg^{2+}$). The drug has a significantly higher affinity for this receptor than endogenous magnesium.

By binding to the receptor, the active substance securely blocks the ion channel. This shortens the duration for which calcium ions ($Ca^{2+}$) can enter the nerve cell. This intervention results in a pronounced reduction of neuronal membrane depolarization. The main outcome of this process is the prevention of the neurotoxic action of the neurotransmitter glutamate, known in medicine as excitotoxicity (cell damage and death due to overstimulation).

Additional targets and clinical effects

Although NMDA receptors are the primary target, the drug also actively interacts with other structures of the nervous system. Specifically, it affects nicotinic acetylcholine receptors (a specific type of alpha-7nAChR) and serotonin receptors (5-HT3 type). This complex action is believed to make a significant contribution to the overall therapeutic effect.

At the level of clinical manifestations, pharmacodynamic effects are expressed as follows:

• There is a moderate restoration of mnemonic functions, meaning the patient's memory improves.
• Various behavioral disorders characteristic of neurodegenerative processes are corrected.
• The patient's ability to perform daily self-care significantly increases, which considerably facilitates caregiving.

The prospects of using this agent in other central nervous system pathologies besides dementia are currently under active investigation.

Indications and adverse reactions

The primary and main indication for prescribing the drug is Alzheimer's type dementia at moderate to severe stages.

Despite proven efficacy, therapy may be accompanied by a number of side effects affecting various organ systems:

• Central nervous system: reactions can be either depressing (onset of lethargy, dizziness) or paradoxically stimulating (development of agitation, insomnia, and even hallucinations).
• Cardiovascular system: increase in blood pressure and development of hypertension are possible.
• Urinary system: cases of cystitis developing during treatment have been reported.

Metabolic cerebroprotectants

In the context of psychotropic drugs and agents that improve brain function, it is also important to mention the group of metabolic cerebroprotectants. Typical representatives of this group include hopantenic acid and pyrithinol.

The general characteristic of these medications includes a pronounced antihypoxic effect (increasing tissue resistance to oxygen deprivation) and the ability to qualitatively improve metabolism in nervous tissue. An important advantage of this group is a wide therapeutic window, indicating high safety of use.

Special attention should be given to pyrithinol (trade name Encephabol). Chemically, this compound consists of two vitamin B6 (pyridoxine) molecules connected by a disulfide bridge. Due to this structural similarity, the drug requires strict precautions: it must be used with extreme caution in patients with a history of allergy or hypersensitivity to pyridoxine.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• The role of glutamate and NMDA receptors in the pathogenesis of Alzheimer's disease
• The mechanism of excitotoxicity development in nervous tissue
• The effect of psychotropic drugs on serotonin (5-HT3) and nicotinic receptors
• Pharmacology of metabolic cerebroprotectants (hopantenic acid)

Other topics in the section "Agents Used in Psychiatry and Neurology"

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