Analgesic potency of alpha adrenergic agents after systemic administration in amphibians

The analgesic and behavioral effects produced by systemic adrenergic agonists dexmedetomidine (0.1-3 nmol/g), clonidine (100-1000 nmol/g), epinephrine (1-30 nmol/g) and norepinephrine (10-300 nmol/g) were determined in Rana pipiens using the acetic acid test. Each agonist produced a dose-dependent analgesic effect that was sustained for at least 4 hr with all agonists. The analgesic effect of epinephrine and dexmedetomidine was observed 15 min after agonist administration and continued for more than 8 hr. Dexmedetomidine was the most potent agonist followed by epinephrine, norepinephrine and clonidine, and the relative potencies compared to epinephrine = 1.0 were 0.01 (clonidine), 0.02 (norepinephrine) and 4.83 (dexmedetomidine). Pretreatment with selective alpha-2 receptor antagonists, yohimbine and atipamezole, significantly decreased the analgesic effect of dexmedetomidine (80 and 87%) and clonidine (66 and 60%), whereas the selective alpha-1 receptor antagonist, prazosin, had no effect on dexmedetomidine but augmented clonidine analgesia. All animals treated with alpha adrenergic agonists retained corneal, righting and hind limb withdrawal reflexes and exhibited normal behavior. These studies demonstrate that systemic adrenergic agonists produce analgesia in amphibians, with a similar order of potency as reported in mammalian studies, and suggest that this analgesia is mediated by adrenergic alpha-2 receptors.