Effects of radolmidine, a novel alpha(2-)adrenergic agonist compared with dexmedetomidine in different pain models in the rat

Background: Intrathecally administered alpha(2)-adrenoceptor agonists produ ce effective antinociception, but sedation is an important adverse effect. Radolmidine is a novel alpha(2)-adrenoceptor agonist with a different pharm acokinetic profile compared with the well-researched dexmedetomidine, This study determined the antinociceptive and sedative effects of radoimidine in different models of acute and chronic pain. Dexmedetomidine and saline ser ved as controls. Methods: Male Sprague-Dawley rats were studied in acute pain (tail flick), carrageenan inflammation, and the spinal nerve ligation model of neuropathi c pain. Mechanical allodynia was assessed with von Frey filaments, cold all odynia with the acetone test, and thermal hyperalgesia with the paw flick t est. Locomotor activity-vigilance was assessed in a dark field. Dexmedetomi dine and radolmidine were administered intrathecally In doses of 0.25 mu g, 2.5 mu g, 5 mu g, and 10 mu g. Results: In the tail flick test, radolmidine showed a dose-dependent antino ciceptive effect, being equipotent compared with dexmedetomidine. In carrag eenan Inflammation, intrathecal doses of 2.5 pb or 5 mu g of dexmedetomidin e/radolmidine produced significant antinociception compared with saline (P < 0.01). The two drugs were equianalgesic. In the neuropathic pain model, a n intrathecal dose of 5 mu g dexmedetomidine-radolmidine had a significant antiallodynic effect compared with saline (P < 0.01). The two drugs were eq uipotent. Intrathecal administration of both dexmedetomidine and radolmidin e dose dependently decreased spontaneous locomotor acitivity-vigilance, but this effect was significantly smaller after intrathecal administration of radolmidine than after intrathecal dexmedetomidine. Conclusions: Radolmidine and dexmedetomidine had equipotent antinociceptive effects in all tests studied. However, radolmidine caused significantly le ss sedation than dexmedetomidine, probably because of a different pharmacok inetic profile.