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Salbutamol Effects in Asthma and Parkinson’s Disease Risk

Linda Crampton is an experienced teacher with a first-class honors degree in biology. She writes about the scientific basis of disease.

A typical salbutamol, albuterol, or Ventolin inhaler

A typical salbutamol, albuterol, or Ventolin inhaler

Salbutamol in Rescue or Reliever Inhalers

Salbutamol (also known as albuterol) is an inhaled medication that is prescribed to open up the airways during an asthma attack. It's also used in COPD, or chronic obstructive pulmonary disease. A common brand name of the medication is Ventolin. Salbutamol can be a vital treatment when breathing becomes difficult. The chemical’s benefits may extend beyond the respiratory system, however. A research team at the Harvard Medical School has discovered that salbutamol intake appears to reduce the risk of Parkinson’s disease development. Further research is required to confirm this interesting and perhaps important idea.

Salbutamol is traditionally delivered from a blue inhaler, which is sometimes called a rescue or a reliever inhaler. The medication is contained in a canister. The top of the canister must be pressed in order the release the drug in aerosol form through the mouthpiece of the inhaler.

Using a salbutamol inhaler

Using a salbutamol inhaler

What Is Asthma?

Asthma is a chronic disorder in which the airways in the respiratory system are inflamed. The airways are the passageways that transport air to the alveoli, or air sacs, in the lungs. The trachea or windpipe is the widest airway. It leads to a tube called a bronchus (plural: bronchi) in each lung, as shown in the illustration below. Each bronchus branches into narrower bronchi, which in turn branch into tiny bronchioles. The bronchioles send inhaled air to the alveoli. Here oxygen enters the bloodstream. Carbon dioxide leaves the blood and enters the alveoli to be exhaled.

When inflammation flares up during an asthma attack, the tissue lining the airways swells. Another problem is that the glands in the tissue make an excessive amount of mucus, which collects in the airways. These changes reduce the space available for air transport. In addition, the muscles around the outside of the airways tighten, making it difficult for the airways to expand so that they can transport more oxygen. A severe asthma attack can be life threatening and may require emergency medical treatment.

Many people are able to control their symptoms with appropriate medications and the avoidance of their personal triggers for asthma attacks. At the moment, the condition can be treated but not cured. The goal of treatment is to find a regimen that eliminates the attacks. My personal regimen controls my asthma well, but occasionally I need to use my salbutamol inhaler.

The airways include the trachea, bronchi, and bronchioles.

The airways include the trachea, bronchi, and bronchioles.

Asthmatics often use a maintenance inhaler containing a corticosteroid every day in order to reduce inflammation in their airways, as I currently do. This decreases the chance of an asthma attack (and may even prevent any attacks) as well as the need to use the rescue inhaler.

How Does Salbutamol Relieve Asthma?

Salbutamol is classified as a beta-2 adrenergic receptor agonist. A receptor is a protein on or in the cell membrane that binds to specific chemicals that come into contact with the cell. As a result of the union, the receptor is activated and a particular process is triggered. An agonist is a chemical that activates a receptor. Adrenergic receptors got their name because they are stimulated by epinephrine, which is also known as adrenaline.

The ability of salbutamol to activate the beta-2 type of adrenergic receptor is the basis of its benefits in asthma, COPD, and possibly in respect to Parkinson’s disease as well. The receptor is also known as a β2-adrenoreceptor or as β2AR. It's common in the muscles around the airways. Salbutamol's activation of the receptor causes relaxation of the muscles. This enables the airways to widen, which makes breathing easier.

Salbutamol often works very well without side effects. Sometimes side effects do appear, however. These may include a rapid heartbeat, shakiness, headache, and/or muscle cramps. I've experienced a rapid heartbeat, but only when I've taken too much salbutamol in a short period of time. Occasionally, the side effects of salbutamol use may be serious. Instructions for using the medicine must be followed carefully and a doctor's advice sought if problems develop.

A beta-2 adrenergic receptor in the cell membrane

A beta-2 adrenergic receptor in the cell membrane

A cell membrane contains two rows of phospholipid molecules, which are the orange structures in the simplified illustration of a membrane shown above. The green structure is the receptor. Like other proteins, it has a highly folded structure.

What Is Parkinson's Disease?

Parkinson's disease is a neurodegenerative condition. A characteristic of the disease is the collection of tangled fibres of a protein called alpha-synuclein in the brain. The tangles join to other substances to form structures called Lewy bodies. These bodies often appear in a region of the brain known as the substantia nigra.

Brain cells in the substantia nigra die when Lewy bodies are present. The living cells make a neurotransmitter called dopamine. A neurotransmitter is a substance that influences the passage of nerve impulses from one neuron (nerve cell) to another. Dopamine is involved in a variety of processes in the body, including the control of movement. Loss of dopamine leads to movement problems, balance problems, and muscle tremors in people with Parkinson's disease. The disease can't be cured at the moment, but it can be helped by a variety of treatments.

It's not completely clear whether tangled alpha-synuclein is the cause of Parkinson's disease or the result, but many researchers seem to feel that it's more likely to be the cause. Scientists have been searching for a way to break Lewy bodies down or to trigger the body to get rid of them. The Harvard researchers decided to look for a way to reduce the amount of alpha-synuclein that's made instead. The protein is a normal component of our body, so it mustn't be completely eliminated.

In Parkinson's disease, cells in the substantia nigra die.

In Parkinson's disease, cells in the substantia nigra die.

Individuals who inhaled the highest doses of salbutamol were about half as likely to develop the devastating neurological condition as those who didn’t take the drug.

— Mitch Leslie, Science (an AAAS publication)

Salbutamol and Parkinson's Disease Risk

The interesting and perhaps very significant research linking salbutamol to Parkinson's disease reduction was performed at the Harvard Medical School in Boston. In the first stage of the research, the scientists grew human nerve cells in the lab. They then tested more than 1100 chemicals to see if they reduced the amount of alpha-synuclein that was produced by the cells. The chemicals that were tested included dietary supplements, herbal compounds, and medications.

Several activators of β2-adrenoreceptors were found to be effective at reducing the alpha-synuclein level, including salbutamol. A hypertension drug named propranolol increased the amount of alpha-synuclein, however. This fact may be significant because the drug inhibits the activity of β2-adrenoreceptors. Inhibitors of receptors are called antagonists.

In the second stage of the research, the scientists examined a large Norwegian database with the aid of a scientist from the University of Bergen. The database contained the prescription records of 4.6 million people. The researchers analyzed the records of people who had been prescribed salbutamol during a period of eleven years (2004 to 2014). The identity of the people wasn't revealed. Results varied based on how often a patient was prescribed the medication, but overall the researchers found that a person taking salbutamol was one third less likely to develop Parkinson's disease during the eleven years of the study.

Structure of the two slightly different forms of salbutamol; carbon atoms are black, hydrogen white, oxygen red, and nitrogen blue

Structure of the two slightly different forms of salbutamol; carbon atoms are black, hydrogen white, oxygen red, and nitrogen blue

Warning

People mustn't take extra salbutamol, start taking the drug, or take the clenbuterol mentioned below in an attempt to prevent Parkinson's disease. The medicines can have potentially serious side effects if they are taken in excess of the body's needs. It's also important that people continue to take prescribed medicines known as beta-blockers. These stop certain chemicals from binding to beta-2 adrenergic receptors.

Interesting Research Using Clenbuterol

The research into how salbutamol influences the risk of Parkinson's disease is still in its very early stages. One possible clue has been discovered. It may or may not apply to salbutamol. It was discovered by testing a different bronchodilator and β2-adrenoreceptor agonist (clenbuterol). This was one of the successul chemicals in the first stage of the Harvard research.

The Harvard researchers used mouse cells and isolated human cells in their study. They found that when β2-adrenoreceptors in the cells were activated by clenbuterol, the gene containing instructions for making alpha-synuclein was inhibited. Genes are located in our DNA (deoxyribonucleic acid), which is in turn located in the nucleus of the cell. They contain the code for making proteins.

What Is a Clinical Trial?

Caution When Interpreting Survey Results

The results of the Harvard survey are fascinating and potentially very important. A survey can't prove that a chemical has a health benefit, however, although it can suggest that this is possible or even likely. The larger the database that is studied, the more likely that the conclusions are true. A clinical trial is necessary to demonstrate that a discovery is correct. In this type of experiment, a treatment is administered to volunteers under conditions that are as much as possible controlled. The effects of the treatment are then studied in detail.

Some points to consider when analyzing the Harvard research include the following:

  • The people in the Harvard and Norwegian survey who appeared to have been helped by salbutamol may actually have benefited due to a factor that is sometimes associated with salbutamol use and not from the medication itself. (Some scientists suspect that this may have been the case.)
  • It's possible that people need a certain gene variant or variants before they can benefit from salbutamol's effect on Parkinson's development.
  • People in countries in which people have a different lifestyle and gene variant frequency from Norwegians may show different results.
  • Some people who were free of Parkinson's during the eleven-year-study may have developed the disease at a later date or may develop it in the future, since the survey only included data from 2004 to 2014.

Researchers are trying to find ways to remove protein tangles that have already formed in the brain of people with Parkinson's disease as well as to prevent the tangles from forming.

Hope for the Future

The Harvard research was reported in 2017. I suspect that it's going to take some time and effort to clarify all of the factors involved in salbutamol's influence on the risk of Parkinson's disease. The effort could be very worthwhile. If scientists discover more details about the effects of salbutamol or identify a different reason for a reduced risk of Parkinson's disease, it's possible that in the future many people could be protected from the illness. It might even be possible to offer people better help if they already have the disease.

The results of the Harvard research are interesting and exciting. There are unanswered questions linked to the research, however, which is why nobody should change their current medication use without their doctor's recommendation. I hope that more research is performed and that the answers to the questions are discovered as soon as possible.

References

This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2017 Linda Crampton

Comments

Linda Crampton (author) from British Columbia, Canada on April 21, 2020: