5'-Chloro-5'-deoxy-N6-(±)-endo-norbornyladenosine, a potent and highly selective human A1 adenosine receptor agonist modulates neuropathic pain in mice.

A1 adenosine receptors (A1ARs) are promising drug targets for neuropathic pain treatment. Some N6-substituted adenosine derivatives as A1AR agonists have shown to modulate nociception in vivo. Recently, we reported 5'-chloro-5'-deoxy-N6-(±)-endo-norbornyladenosine (5'Cl5'd-(±)-ENBA) as a very potent and highly selective human A1AR agonist with antinociceptive effects in mice.1 This study was undertaken to investigate the effect of 5'Cl5'd-(±)-ENBA on neuropathic pain. Mice with sciatic nerve injury (spared nerve injury, SNI) and combined behavioural, molecular and morphological approaches to assess the involvement of A1ARs in neuropathic pain-associated hyperalgesia, allodynia, spinal cord gliosis and neuro-inflammation, were used. It was found that A1AR stimulation with 5'Cl5'd-(±)-ENBA was capable to protect neuropathic mice from all those SNI-induced modifications. 1. Franchetti, P.; Cappellacci, L.; Vita, P.; Petrelli, R.; Lavecchia, A.; Kachler, S.; Klotz, K.-N.; Marabese, I.; Luongo, L.; Maione, S.; Grifantini, M. J. Med. Chem. published on Web 03/24/2009.