Allergy sufferers can tell you that while antihistamines might ease their plight, they are often too groggy with the side-effects of the drug that it's difficult to enjoy their sneeze relief. Now, thanks to some sleuth work by a team of international scientists, the complex 3-D structure of the human histamine H1 receptor protein has been cracked, which could pave the way for antihistamines with fewer side-effects.
First, some more about the H1 receptor protein. It binds to histamine and is found is various tissues in the body, including the brain, and plays an important role in the immune system. But in some susceptible people, it can cause allergic reactions like hay fever and pet allergies. What antihistamines do is block histamines from attaching to H1 receptors.
"First-generation antihistamines such as doxepin are effective, but not very selective, and because of penetration across the blood-brain barrier, they can cause side-effects including sedation, dry mouth and arrhythmia," Simone Weyand, postdoctoral scientist at Imperial College London, said in a release. "By showing exactly how histamines bind to the H1 receptor at the molecular level, we can design and develop much more targeted treatments."
The scientists, using Diamond Light Source, the UK's national synchrotron facility, have paved the way for development of "third-generation" antihistamines that can be tailored to specific allergies without side-effects.
"It took a considerable team effort but we were finally able to elucidate the molecular structure of the histamine H1 receptor protein and also see how it interacts with antihistamines," So Iwata, director of the Membrane Protein Laboratory at Diamond, said in a release. "This detailed structural information is a great starting point for exploring exactly how histamine triggers allergic reactions and how drugs act to prevent this reaction."
- read the release
- and the abstract in Nature