Targetting adenosine A1 receptor (A1R) down regulation could be a new therapeutic strategy for restless leg syndrome (RLS), according to preclinical findings in a rat model and clinical results in humans, published in Journal of Caffeine and Adenosine Research, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.
Periodic limb movements and the state of enhanced arousal will disrupt sleep in RLS. It is a common disorder, with about 5% of individuals in the U.S. and Europe reporting symptoms, as described in the article "The Adenosine Hypothesis of Restless Legs Syndrome".
‘The Biochemical link that could serve as a new promising approach for the common sleep disorder restless leg syndrome is adenosine. Targeting the receptor down regulation could address the issue.’
More than one pathogenetic mechanism likely underlies the spinal cord-related and non-spinal cord-related aspects of the disorder, and researchers have long looked for a biochemical link that could serve as a new therapeutic target.
A combination of preclinical and clinical findings has shown that brain iron deficiency (BID) is an early factor in the pathophysiology of RLS and that BID in rodents causes down regulation of A1Rs in the brain.
"Based on these results," Editor-in-Chief of Journal of Caffeine and Adenosine Research, Sergi Ferré, MD, PhD, and his research colleagues in the Integrative Neurobiology Section, National Institute on Drug Abuse, National Institutes of Health (Baltimore, MD), "have hypothesized that a hypoadenosinergic state secondary to A1R down regulation could be mostly responsible for the hyperglutamatergic and hyperdopaminergic states of RLS that determine the sensorimotor symptoms of RLS as well as the hyperarousal component." They add, "We, therefore, predicted that inhibitors of equilibrative nucleoside transporters, by increasing the striatal extra-cellular levels of adenosine, could provide a new therapeutic approach for RLS."