About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Research Highlights New Understanding of Sulfonamide Nervous System Side Effects

by Kathy Jones on May 26, 2013 at 8:11 PM
Font : A-A+

 Research Highlights New Understanding of Sulfonamide Nervous System Side Effects

Sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections ever since the discovery of Prontosil in 1932.

However, their side effects can include serious neurological problems like nausea, headache, dizziness, hallucinations and even psychosis. In a recent Science publication, EPFL researchers have shown for the first time how sulfonamides can interfere with a patient's nervous system.

Advertisement

The problem is that, even though we know how sulfonamides work, we do not understand the actual molecular mechanics behind their side effects. Consequently, it is difficult to modify drug structure or customize therapeutic regimes in order to better serve the needs of patients. That is the critical issue addressed by a team of EPFL scientists lead by Kai Johnsson at EPFL's Laboratory of Protein Engineering.

The team drew from previous research showing that blocking the activity of a certain enzyme (sepiapterin reductase) affects the levels of an important molecule called tetrahydrobiopterin (BH4) in cells. BH4 is critical for the production of neurotransmitters like serotonin and dopamine, and BH4 deficiency causes similar neurological problems to those associated with sulfonamide side effects.
Advertisement

The EPFL scientists showed for the first time that sulfonamides actually bind to the part of the enzyme that makes BH4. Using a high-throughput drug screening system, the researchers identified ten sulfonamides that strongly inhibit the enzyme. Taking advantage of the expertise of Florence Pojer at EPFL's Global Health Institute, the scientists were able to solve the enzyme's molecular structure and determine how sulfonamides bind to it.

Sulfonamides also seem to act on the actual biochemical pathway that synthesizes BH4, as increasing doses of the drugs decreased BH4 concentrations in cultured human cells. The critical finding, however, was that, along with BH4, sulfonamides also reduced the actual production of dopamine. By giving cultured human nerve cells different sulfonamides, the researchers found that their natural production of dopamine decreased in proportion to the sulfonamide doses. In addition, it was clear that the impact on dopamine production was different between sulfonamides.

The group's work shows for the first time that sulfonamides interfere with the biosynthesis of neurotransmitters, which can account for their reported neurological side effects. It also helps us understand how the activity of these drugs relates to their molecular structure, and suggests ways of improving their clinical use.

"Once you know what's happening you can begin to think about strategies to address the problem - and that is the impact of this work", says Kai Johnsson. "Historically, I don't think that there is a more important class of drugs than sulfonamides, and now we can understand them better. It also reminds us that surprising discoveries can be made even for drugs this old."



Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Advertisement
News Category
What's New on Medindia
Memory Loss - Can it be Recovered?
International Day of Persons with Disabilities 2021 - Fighting for Rights in the Post-COVID Era
Effect of Blood Group Type on COVID-19 Risk and Severity
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Aphasia Ataxia 

Recommended Reading
Drugs Banned in India
Several drugs are either banned or withdrawn after introduction in the market....
Drugs Causing Low Blood Sodium Levels / Hyponatremia
Many drugs can lower your blood sodium levels or hyponatremia. Low blood sodium symptoms are ......
Drugs in Pregnancy and Lactation
During pregnancy & lactation a nutritious diet, suitable exercise, adequate rest and a tranquil ......
Aphasia
Aphasia is a condition where the patient has a language disorder. The patient has problems with comp...
Ataxia
Ataxia affects coordination. Gait becomes unstable and the patient loses balance. The cerebellum or ...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use