For the first time in the world, a research group at the International Institute for Integrative Sleep Medicine, University of Tsukuba, has shown that A2AR PAM-2, a novel low-molecular-weight compound that enhances signals from adenosine A1A receptors, promotes near-natural sleep.
Currently, it is said that 10 to 15% of the population (30 to 60% of the elderly) suffer from insomnia.Insomnia is mainly treated with drugs, but the side effects of existing sleeping pills are often a problem.The most common benzodiazepine and non-benzodiazepine hypnotics have been pointed out as having side effects such as light-headedness and dizziness, as well as the risk of addiction.There is a need to develop a drug with a new mechanism of action that eliminates these side effects and promotes a more natural sleep.
Therefore, this research group focused on adenosine, which is known to induce sleep in the brain.Adenosine A2A receptor agonists have shown a strong hypnotic effect in previous studies, but at the same time, there have been problems with cardiovascular side effects such as decreased body temperature, hypotension and tachycardia.Therefore, the group focused on "Positive Allosteric Modulators" that act on sites different from the ligand binding site of the receptor and enhance their signals, and after screening the pharmacological activity of more than 1,000 types of small molecule compounds, they are new. The small molecule compound A2AR PAM-1 was identified for the first time in the world.When this compound was administered intraperitoneally to mice, it succeeded in inducing slow-wave sleep without lowering body temperature or side effects of the circulatory system.
This result is expected to develop a therapeutic drug for insomnia with a new mechanism of action that is different from conventional hypnotics.
