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

Scientists find key to regenerating blood vessels

November 23, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) identifies a signaling pathway that is essential for angiogenesis, the growth of new blood vessels from pre-existing vessels. The ...

Researchers find infectious prions in Creutzfeldt-Jakob disease patient skin

November 22, 2017
Creutzfeldt-Jakob disease (CJD)—the human equivalent of mad cow disease—is caused by rogue, misfolded protein aggregates termed prions, which are infectious and cause fatal damages in the patient's brain. CJD patients ...

Surprising roles for muscle in tissue regeneration, study finds

November 22, 2017
A team of researchers at Whitehead has illuminated an important role for different subtypes of muscle cells in orchestrating the process of tissue regeneration. In a paper published in the November 22 issue of Nature, they ...

Study reveals new mechanisms of cell death in neurodegenerative disorders

November 22, 2017
Researchers at King's College London have discovered new mechanisms of cell death, which may be involved in debilitating neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

How rogue immune cells cross the blood-brain barrier to cause multiple sclerosis

November 21, 2017
Drug designers working on therapeutics against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons, according to a new study in the journal Cell Reports.

New simple test could help cystic fibrosis patients find best treatment

November 21, 2017
Several cutting-edge treatments have become available in recent years to correct the debilitating chronic lung congestion associated with cystic fibrosis. While the new drugs are life-changing for some patients, they do not ...

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.