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

• Published in: British journal of pharmacology 2010-08, Vol.160 (7), p.1662
• Main Authors: Kosugi, Toshifumi, Mizuta, Kotaro, Fujita, Tsugumi, Nakashima, Mikio, Kumamoto, Eiichi
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Agonists - chemistry; Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Animals; Dexmedetomidine - chemistry; Dexmedetomidine - pharmacology; Dose-Response Relationship, Drug; In Vitro Techniques; Molecular Structure; Ranidae; Sciatic Nerve - drug effects; Sciatic Nerve - metabolism; Sciatic Nerve - physiology
• ISSN: 1476-5381
• DOI: 10.1111/j.1476-5381.2010.00833.x

Dexmedetomidine, an alpha(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. 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. Dexmedetomidine reversibly and concentration-dependently reduced the peak amplitude of CAPs (IC(50)= 0.40 mmol x L(-1)). This action was not antagonized by two alpha(2)-adrenoceptor antagonists, yohimbine and atipamezole; the latter antagonist itself reduced CAP peak amplitude. Clonidine and oxymetazoline, two other alpha(2)-adrenoceptor agonists, also inhibited CAPs; the maximum effect of clonidine was only 20%, while oxymetazoline was less potent (IC(50)= 1.5 mmol x L(-1)) than dexmedetomidine. On the other hand, (+/-)-adrenaline, (+/-)-noradrenaline, alpha(1)-adrenoceptor agonist (-)-phenylephrine and beta-adrenoceptor agonist (-)-isoprenaline (each 1 mmol x L(-1)) had no effect on CAPs. Tetracaine reversibly reduced CAP peak amplitude (IC(50) of 0.014 mmol x L(-1)). Dexmedetomidine reduced CAP peak amplitude without alpha(2)-adrenoceptor activation (at concentrations >1000-fold higher than those used as alpha(2) adrenoceptor agonist), with a lower potency than tetracaine. CAPs were inhibited by other alpha(2) adrenoceptor agonists, oxymetazoline and clonidine, and also an alpha(2) adrenoceptor antagonist atipamezole. Thus, some drugs acting on alpha(2) adrenoceptors are able to block nerve conduction.