High concentrations of dexmedetomidine inhibit compound action potentials in frog sciatic nerves without α 2 adrenoceptor activation

BACKGROUND AND PURPOSE Dexmedetomidine, an α 2 ‐adrenoceptor agonist, exhibits anti‐nociceptive actions at the spinal cord and enhances the effect of local anaesthetics in the peripheral nervous system. Although the latter action may be attributed in part to inhibition of nerve conduction produced by dexmedetomidine, this has not been fully examined yet. EXPERIMENTAL APPROACH We examined the effects of various adrenoceptor agonists including dexmedetomidine, and tetracaine, a local anaesthetic, on compound action potentials (CAPs) recorded from the frog sciatic nerve, using the air‐gap method. KEY RESULTS Dexmedetomidine reversibly and concentration‐dependently reduced the peak amplitude of CAPs (IC 50 = 0.40 mmol·L −1 ). This action was not antagonized by two α 2 ‐adrenoceptor antagonists, yohimbine and atipamezole; the latter antagonist itself reduced CAP peak amplitude. Clonidine and oxymetazoline, two other α 2 ‐adrenoceptor agonists, also inhibited CAPs; the maximum effect of clonidine was only 20%, while oxymetazoline was less potent (IC 50 = 1.5 mmol·L −1 ) than dexmedetomidine. On the other hand, (±)‐adrenaline, (±)‐noradrenaline, α 1 ‐adrenoceptor agonist (‐)‐phenylephrine and β‐adrenoceptor agonist (‐)‐isoprenaline (each 1 mmol·L −1 ) had no effect on CAPs. Tetracaine reversibly reduced CAP peak amplitude (IC 50 of 0.014 mmol·L −1 ). CONCLUSIONS AND IMPLICATIONS Dexmedetomidine reduced CAP peak amplitude without α 2 ‐adrenoceptor activation (at concentrations >1000‐fold higher than those used as α 2 adrenoceptor agonist), with a lower potency than tetracaine. CAPs were inhibited by other α 2 adrenoceptor agonists, oxymetazoline and clonidine, and also an α 2 adrenoceptor antagonist atipamezole. Thus, some drugs acting on α 2 adrenoceptors are able to block nerve conduction.