Optochemistry is a new pharmacologic approach where light helps to activate or deactivate selective molecules. This approach is used to cure diseases, alleviate symptoms and improve quality of life along with preventing uncontrollable drug effects.
Professor Michael Lazarus from the Institute of Medicine with the cooperation of Associate Professor Tsuyoshi Saitoh from the International Institute for Integrative Sleep Medicine (WPI-IIIS) conducted a new research at the University of Tsukuba on optochemistry. It was conducted as part of a research project and funded by the World Premier International Research Center Initiative (WPI), Grants-in-Aid for Scientific Research, and Japan Science and Technology Agency CREST Grant.
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The research aimed to develop a light-sensitive drug with the potential to increase the activity of extracellular adenosine. The drug was administered to mice to induce sleep artificially through selectively irradiating the nucleus accumbens with light for the first time, without any genetic modification.
The nucleus accumbens affects sleep regulation and motivational behaviour, balanced by adenosine A2A receptors (A2AR). Adenosine A2A receptors (A2ARs) were used as the target of this drug as it has a significant influence on the body and central nervous system (CNS). These receptors are scattered across various organs even in the heart. It was a challenge for the researchers to find a brain-specific change without any genetic modulation.
Hence, sleep and motivation could be controlled by selective regulation of A2AR within this brain region.
Traditional photosensitive drugs cause side effects in mammals and other living organisms. Problems like photoreaction efficiency, phototoxicity caused by ultraviolet light and blood-brain barrier permeability can occur as a result of using these drugs. But the new photosensitive drug has successfully overcome these barriers proving the potentiality of optochemistry in developing drugs that can target A2AR in the brain. This can also target other central drug receptors and regulate brain function.
References +
- Neuroscience News. (2024, May 28). Light-Activated drug induces sleep by targeting brain receptors. https://neurosciencenews.com/sleep-light-activated-neuropharmacology-26187/
- Roy, K., Zhou, X., Otani, R., Yuan, P., Ioka, S., Vogt, K. E., Kondo, T., Farag, N. H. T., Ijiri, H., Wu, Z., Chitose, Y., Amezawa, M., Uygun, D. S., Cherasse, Y., Nagase, H., Li, Y., Yanagisawa, M., Abe, M., Basheer, R., . . . Lazarus, M. (2024). Optochemical control of slow-wave sleep in the nucleus accumbens of male mice by a photoactivatable allosteric modulator of adenosine A2A receptors. Nature Communications, 15(1). https://doi.org/10.1038/s41467-024-47964-4
