Effects of radolmidine, a novel α2-adrenergic agonist compared with dexmedetomidine in different pain models in the rat

Background: Intrathecally administered alpha(2)-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Radolmidine is a novel alpha(2)-adrenoceptor agonist with a different pharmacokinetic 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 served as controls. Methods: Male Sprague-Dawley rats were studied in acute pain (tail flick), carrageenan inflammation, and the spinal nerve ligation model of neuropathic pain. Mechanical allodynia was assessed with von Frey filaments, cold allodynia with the acetone test, and thermal hyperalgesia with the paw flick test. Locomotor activity-vigilance was assessed in a dark field. Dexmedetomidine 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 antinociceptive effect, being equipotent compared with dexmedetomidine. In carrageenan Inflammation, intrathecal doses of 2.5 pb or 5 mu g of dexmedetomidine/radolmidine produced significant antinociception compared with saline (P < 0.01). The two drugs were equianalgesic. In the neuropathic pain model, an intrathecal dose of 5 mu g dexmedetomidine-radolmidine had a significant antiallodynic effect compared with saline (P < 0.01). The two drugs were equipotent. Intrathecal administration of both dexmedetomidine and radolmidine 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 less sedation than dexmedetomidine, probably because of a different pharmacokinetic profile.