Researchers move closer to understanding the biology behind gamma-hydroxybutyric acid

July 2, 2012

In the 1960s, gamma-hydroxybutyric acid (GHB) was first discovered as a naturally occurring substance in the brain. Since then it has been manufactured as a drug with a clinical application and has also developed a reputation as the illegal drug fantasy and as a date rape drug. Its physiological function is still unknown.

Now a team of researchers at the Department of Design and Pharmacology at the University of Copenhagen has shown for the first time exactly where the transmitter substance binds in the brain under physiologically relevant conditions. The results have recently been published in the scientific journal PNAS ().

"We have discovered that GHB binds to a special in the brain – more specifically a GABAA-receptor. The binding is strong even at very low dosage. This suggests that we have found the natural receptor, which opens new and exciting research opportunities, in that we have identified an important unknown that can provide the basis for a full explanation of the biological significance of the transmitter," says Laura Friis Eghorn, PhD student.

Fantasy is also used as a so-called date rape drug, because in moderate amounts it has sedative, sexually stimulating and soporific effects. The compound is also abused for its euphoric effect, but in combination with alcohol, for example, it is a deadly cocktail that can lead to a state of deep unconsciousness or coma.

"GHB is registered for use as a drug to treat alcoholism and certain types of sleep disorders, but the risk of abuse presents difficulties. In the long-term, understanding how GHB works will enable us to develop new and better pharmaceuticals with a targeted effect in the brain, without the dangerous side-effects of fantasy," explains Laura Friis Eghorn, Department of Drug Design and .

Fantasy is an extremely toxic euphoriant, because the difference between a normal intoxicating dose and a fatal dose is so small. A better understanding of the biological mechanisms behind GHB-binding in the brain will benefit research into a life-saving antidote for this drug. Today there is no known antidote.

Statistics from Denmark in 2010 show that 8-10 percent of young people who frequent night clubs have had experience with Fantasy. However, since the drug is often also used in private for its sedative effect, it is difficult to estimate the extent of abuse.

The new research findings are the result of a collaboration between researchers at the University of Sydney in Australia and medicinal chemists at the Faculty of Health and Medical Sciences:

"Our chemist colleagues designed and produced special ligands – that are mimics of GHB in several variations. This enabled us to go on a targeted fishing expedition in the brain. We have slowly found our way to the receptor, which we have also been able to test pharmacologically. In itself, it is not unusual to find new receptors in the for known compounds. However, when we find a natural match rooted in the brain's transmitter system, the biological implications are extremely interesting," explains Petrine Wellendorph, associate professor and head of the responsible research group that produced the pioneering results.

Explore further: Promising new compound for treating stroke

Related Stories

Promising new compound for treating stroke

February 21, 2012
Researchers at the University of Copenhagen have designed, produced and patented a new chemical compound for the possible treatment of brain damage caused by stroke. The compound binds 1,000 times more effectively to the ...

South African daffodils may be a future cure for depression

June 22, 2012
Scientists at the University of Copenhagen have previously documented that substances from the South African plant species Crinum and Cyrtanthus – akin to snowdrops and daffodils – have an effect on the mechanisms ...

New piece to the puzzle of brain function

August 19, 2011
Researchers at the Faculty of Pharmaceutical Sciences at the University of Copenhagen have collaborated with the company NeuroSearch to generate new knowledge about an important part of the brain's complex communication system. ...

New knowledge on the pharmacology of dopamine stabilizers

February 24, 2012
A study from Karolinska Institutet in Sweden shows that a new drug for Huntington's disease – pridopidine or dopamine stabiliser ACR16 – might operate via previously unknown mechanisms of action. Researchers have ...

Scientists map new mechanism in brain's barrier tissue

March 8, 2012
Researchers at the University of Copenhagen have documented a previously unknown biological mechanism in the brain's most important line of defence: the blood-brain barrier. Scientists now know that the barrier helps maintain ...

Recommended for you

Synthetic hydrogels deliver cells to repair intestinal injuries

October 23, 2017
By combining engineered polymeric materials known as hydrogels with complex intestinal tissue known as organoids - made from human pluripotent stem cells - researchers have taken an important step toward creating a new technology ...

Study reveals connection between microbiome and autoimmune disorders

October 23, 2017
Many people associate the word "bacteria" with something dirty and disgusting. Dr. Pere Santamaria disagrees. Called the microbiome, the bacteria in our bodies have all kinds of positive effects on our health, Santamaria ...

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.