Amantadine is an organic chemical compound that is used as an antiviral drug and is now used to treat Parkinson's. How does amantadine work? When is it used? What are the side effects of amantadine?

Amantadinehas been introduced into medicine as an antiviral drug. The indication for the use of this substance is the prevention and treatment of infections caused by influenza A virus. It is extremely important that this drug is not active against other types of influenza virus. Currently, the use of amantadine in the treatment of infections is abandoned due to the high resistance of microorganisms to this substance.

The antiviral action of the drug is based on blocking the M2 channel protein on the surface of the virus. It can be said that amantadine forms a kind of plug in the protein channel.

The M2 protein is used to transport hydrogen ions, i.e. to generate an acidic pH necessary to break the envelope protecting the viral genetic material. As a consequence of the action of the drug, the release of genetic material from the envelope is prevented. As a result, microorganisms cannot multiply in the host's organism.

Amantadine has been replaced in medicine by rimantadine, which is characterized by a similar therapeutic mechanism, with reduced side effects.

Amantadine in Parkinson's disease treatment

The therapeutic efficacy of amantadine in Parkinson's therapy was discovered in 1968 by accident. A patient with moderate symptoms of the disease took the drug for three months to prevent flu. Her doctor, Schwab, observed and described a significant reduction in symptoms such as tremors, stiffness and slowness in the affected woman during this treatment. The improvement subsided after some time after discontinuation of amantadine.

A year later, Schwab published the results of clinical trials on the use of amantadine in the therapy of Parkinson's patients. They showed that the daily dose of 200 mg of this drug significantly reduced the symptoms of the disease in 66% of patients. The doctor also noticed a significant improvement in intellectual performance.

Amantadine - the mechanism of action of amantadine in neurological disorders

The mechanism of therapeutic activity of amantadine in neurological diseases is not fully understood. Research suggests thatthere are more than one route of activity for this drug. One of them is the stimulation of dopaminergic conductivity.

During Parkinson's disease, a decrease in the concentration of dopamine in the substantia nigra of the brain is observed. This results in motor disturbances such as slower movements, tremors, and body stiffness.

Amantadine stimulates the release of dopamine from presynaptic terminals. It also inhibits the reuptake of this neurotransmitter and stimulates dopaminergic receptors.

In addition, amantadine blocks the ionotropic NMDA receptor and has a cholinolytic effect. There are theories according to which NMDA receptors and the amino acids stimulating them play an important role in the course of neurodegenerative processes in the brain.

Excessive stimulation of this system leads to ischemia-related neurodegeneration and inflammation. Therefore, amantadine's modulating properties on NMDA receptor activity are therapeutically beneficial.

Amantadine as a cholinolytic drug

Drugs with a cholinolytic effect are those that have an activity that is opposite to the choline neurotransmitter. Many substances used in the treatment of Parkinson's disease have this therapeutic profile. Such drugs are:

  • trihexyphenidyl
  • prydynol
  • biperyden

The mechanism of the cholinolytic action is beneficial in neurodegenerative diseases. Medicines that have it stimulate the nervous system. At the same time, blocking the neurotransmission associated with choline has a relaxing effect on the muscles.

In Parkinson's disease there is increased muscle stiffness, so amantadine's spasmolytic properties, due to its cholinolytic nature, will be beneficial.

Cholinolytics are drugs that strongly affect the entire body. Their acceptance causes:

  • pupil dilation
  • bronchodilation
  • inhibition of intestinal peristalsis
  • dry mouth
  • nervous system agitation leading to hallucinations, agitation, delirium
  • body temperature rise

The listed reactions of the organism to cholinolytic substances may be therapeutically beneficial in certain situations. Unfortunately, however, they often become troublesome side effects.

Drugs with a similar action profile may interact with each other, increasing their negative effect on the body. Therefore, it is not recommended to combine amantadine with other cholinolytics used in the treatment of Parkinson's disease.

Amantadine - neuroprotective and neuromodulating effects

Due to the actionmodulating the activity of NMDA receptors that may participate in neurodegenerative processes, amantadine is effective in inhibiting the development of Parkinson's disease.

These properties have been confirmed in clinical trials lasting 15 years. The life expectancy of patients who took this drug was statistically significantly longer than that of other Parkinson's patients.

Amantadine inhibits inflammatory processes and stimulates growth factors within the nervous system. Therefore, it can be used as a neuroprotective and neuromodulating drug in the early stages of Parkinson's disease.

Amantadine in combination therapy with levodopa

Sustained-release amantadine is used to treat dyskinesias, a side effect of levodopa, which is currently the primary and most important drug in Parkinson's therapy.

Dyskinesias are a problem characteristic of the advanced stage of the disease development. They consist of movement disorders associated with the peak concentration of levodopa in the blood and its subsequent decrease.

The World He alth Organization now recommends the use of amantadine in combination therapy to reduce the side effects of levodopa. At the same time, WHO recognized monotherapy with this drug as an ineffective treatment option.

Amantadine - side effects

There are some central nervous system side effects associated with the use of amantadine. Patients often experience dizziness and hallucinations. They can contribute to uncontrolled falls leading to injury.

Another group of side effects is related to the cholinolytic nature of the drug. Patients taking amantadine may suffer from constipation and dry mouth.

The anticholinergic effect is also associated with the risk of enhancing psychotic behavior in patients with such predisposition.

Serious side effects may include:

  • sleepiness
  • suicidal thoughts
  • depression
  • hallucinations
  • destructive actions leading to addiction: gambling, risky sexual activity, irrational spending
  • self-control problems
  • low blood pressure
  • Stevens-Johnson syndrome

Amantadine - contraindications to use

The main contraindications for taking amantadine are:

  • severe congestive heart failure
  • cardiomyopathy
  • myocarditis,
  • bradycardia
  • heart abnormalities associated with prolonged intervalQT
  • family history of congenital syndrome of long QT interval
  • severe ventricular arrhythmias
  • use of drugs that prolong the QT interval
  • epilepsy
  • hypokalemia
  • hypomagnesaemia
  • pregnancy
  • breastfeeding period

Due to the anticholinergic nature of the drug, people suffering from:

should exercise particular caution when taking amantadine
  • prostate enlargement
  • glaucoma
  • exogenous psychoses

Amantadine - indications for discontinuation of therapy

The use of amantadine should be discontinued in the event of:

  • palpitations
  • faint
  • dizziness

The drug should not be discontinued abruptly in patients taking concomitant neuroleptics. The decision to interrupt or continue treatment should be consulted with a specialist physician.

Amantadine - interactions with other drugs

When taking amantadine, be careful when taking medications:

  • anticholinergics
  • antidepressants
  • anti-discriminatory
  • antihistamines
  • phenothiazine derivatives

Serious interactions of amantadine with other drugs

Amantadine increases the side effects of cholinolytic drugs. This combination can cause hallucinations and confusional states.

It is contraindicated to combine it with drugs that prolong the QT interval. The interaction can lead to serious heart problems.

CNS stimulants in combination with amantadine increase the risk of side effects such as anxiety, nervousness, insomnia and heart problems.

Triamterene and hydrochlorothiazide can lead to dangerous increases in blood levels of amantadine.

Amantadine and COVID-19 treatment. Does Amantadine Work Against Coronavirus?

Every now and then there are reports in the media about the effectiveness of amantadine in COVID-19 treatment. However, as emphasized in an interview with the Polish Press Agency, the head of the Department of Infectious Diseases at the Clinical Hospital No. 1 in Lublin, prof. dr hab. Krzysztof Tomasiewicz, amantadine has no recommendations from organizations that allow drugs for use in therapy.

There is also no evidence that this drug works, and it hasn't been used for a long time. He admitted that various drugs have been used in the treatment of COVID-19 since the beginning of the epidemic, but amantadine was not taken into account. - We had a stage when we considered drugs that work, for example, in the treatment of HIV or chloroquine, because there were grounds, even theoretical, for the use of thesedrugs. In the case of amantadine, there was no such basis and there is no such basis - emphasized the professor.

Prof. Tomasiewicz reminded that legal consequences may be incurred for the use of a drug that is inconsistent with the Summary of Product Characteristics and it is unacceptable.

- Yes, sometimes we decide to undergo experimental therapy, but before that we have to get the approval of the bioethics committee. We have been doing this since the beginning of the COVID-19 epidemic. For example, we use tocilizumab, and before that, remdesivir, which has only been approved for COVID-19 therapy for some time, he said.

He also noticed that the use of drugs that did not help actually postpones the moment of administering the appropriate therapies.

About the authorSara Janowska, MA in pharmacyPhD student of interdisciplinary doctoral studies in the field of pharmaceutical and biomedical sciences at the Medical University of Lublin and the Institute of Biotechnology in Białystok. A graduate of pharmaceutical studies at the Medical University of Lublin with a specialization in Plant Medicine. She obtained a master's degree defending a thesis in the field of pharmaceutical botany on the antioxidant properties of extracts obtained from twenty species of mosses. Currently, in his research work, he deals with the synthesis of new anti-cancer substances and the study of their properties on cancer cell lines. For two years she worked as a master of pharmacy in an open pharmacy.

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