A new therapeutic avenue for treating insomnia

Adenosine has long been known 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. We succeeded in identifying a 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. Allosteric modulators of A2A receptors may help people with sleep problems to fall asleep (Korkutata M., et al., Neuropharmacology, 144: 122-132, 2019). 

 アデノシンはアデノシン受容体を介して睡眠を誘発します。アデノシンA2A受容体作動薬は強力に睡眠を誘発しますが、その一方で心血管作用も示すため、睡眠障害治療薬としての可能性はありません。そこで我々はアデノシンA2A受容体の正のアロステリック調節薬を開発し、それによるA2A受容体シグナルの増強が睡眠を誘発し、かつ心血管系に影響を与えないことを示しました。A2A受容体のアロステリック調節薬は睡眠障害の治療薬へとなりえるかもしれません (Korkutata M., et al., Neuropharmacology, 144: 122-132, 2019)。