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Researchers have discovered a new compound that could potentially treat migraines by blocking light sensors in the eyes, according to a study published in the journal Nature Chemical Biology.
Researchers from the Salk Institute for Biological Studies have found that a series of compounds called opsinamides can block a receptor in the eye called melanopsin - a receptor found in neurons connecting the eyes and the brain.
The researchers discovered 10 years ago that melanopsin is responsible for sensing light on its own, away from normal vision. Continued research found that this receptor is responsible for maintaining sleep cycles and various other sensitivity functions in those with healthy vision.
The receptor was also found to be responsible for constricting the pupil within the eye when it is exposed to bright light, triggering the light-sensitivity that is commonly linked to migraines.
The receptor also picks up on light-sensitivity as we sleep, explaining why sleep patterns can be disrupted if exposed to artificial light during the night.
From this discovery, the researchers believed that if they could find a way to block melanopsin, treatments could be created to prevent and treat migraines.
However, there are other receptors that are closely related to melanopsin - rhodopsin and cone opsins - which are responsible for processing visual information to the brain. Therefore, the researchers needed to create a drug that blocked melanopsin but did not interfere with the other receptors.
For their latest study, the researchers analyzed hundreds of chemicals from the Lundbeck library to see whether each chemical would block melanopsin, and they measured the calcium levels when the receptors were exposed to light.
The study authors say that calcium levels increase in melanopsin when it is exposed to light, signifying that the light has been sensed and that a signal is being sent to the pupil of the eye. A series of chemicals - opsinamides - were found to block the increase in calcium, meaning they were stopping melanopsin from becoming active.
The opsinamides were also showing no interaction with rhodopsin or cone opsins, so the chemicals were tested on mice to measure the psychological response, as well as the effect on their melanopsins.
When the eyes of the mice were exposed to bright light after being treated with one of the compounds, the pupil of the eye did not shrink in size as normally expected, indicating that the compound was blocking the melanopsin receptor.
The opsinamides appeared to have no effect on mice who were lacking melanopsin, meaning that the chemicals were specifically targeting this receptor.
Additionally, when the compounds were tested on newborn mice, they did not avoid bright light - something newborn mice are known for doing before they have even opened their eyes.
Satchidananda Panda, associate professor at the Regulatory Biology Laboratory at the Salk Institute and lead author of the study, says that up until now, everything known about melanopsin has been discovered using inactive mice. This research therefore offers a new way to study the compound.
Kenneth Jones, former project head at Lundbeck, adds:
"The two compounds require further optimization in anticipation of clinical testing but are extraordinarily useful for research purposes and as leads in the discovery process."
The researchers say that one of the co-authors of the study, Jeffrey Spouse, has co-founded a start-up company called Cyanaptic, which will study the compounds further.
Panda adds that once these compounds are further examined and developed, they could be useful to many people in different clinical settings, particularly shift-workers who have disrupted sleep patterns and exposure to sunlight when trying to sleep during the day.
"There are many people who would like to work when they have migraine pain exacerbated by light," adds Panda. "If these drugs could stop the light-sensitivity associated with the headaches, it would enable them to be much more productive."
Written by Honor Whiteman
Copyright: Medical News Today
Not to be reproduced without the permission of Medical News Today.
Small-molecule antagonists of melanopsin-mediated phototransduction published in Nature Chemical Biology, doi:10.1038/nchembio.1333, 25 August 2013.
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