A new therapeutic avenue for treating insomnia

Adenosine has long been known to represent a state of relative energy deficiency and to induce sleep via adenosine receptors. Although adenosine A2A receptor agonists strongly induce sleep, their adverse cardiovascular effects preclude their use in treating sleep disorders. Researchers at the International Institute for Integrative Sleep Medicine (WPI-IIIS) at the University of Tsukuba succeeded in identifying the first positive allosteric modulator for adenosine A2A receptors and demonstrated that enhancing A2A receptor signaling induces sleep that is indistinguishable from the major component of natural sleep, known as slow-wave sleep, as it is characterized by slow and high-voltage brain waves, without affecting cardiovascular function. A positive allosteric modulator may evoke selective physiologic A2A receptor responses because, in contrast to an A2A receptor agonist, its actions are limited to when and where adenosine is released. "We believe that allosteric modulators of A2A receptors may help people with sleep problems to fall asleep" says Mustafa Korkutata, the first author of the paper.

Although mice are the most commonly used model organism of human disease, results in mice, however, are often not always reliable for predicting human study outcomes. Therefore, "many obstacles remain to be overcome in generating a novel drug for the treatment of insomnia in humans, but we believe that our discovery will unlock the development of the next-generation sleeping pill." explained medicinal chemist Dr. Tsuyoshi Saitoh, another lead author of the paper.