title: High concentrations of dexmedetomidine inhibit compound action potentials in frog sciatic nerves without alpha(2) adrenoceptor activation.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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)).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, Saga Medical School, Saga, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Kosugi
authors.forename: Kotaro
authors.initials: K
authors.lastname: Mizuta
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Fujita
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakashima
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kumamoto
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000737:chemistry / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D020927:Dexmedetomidine / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D015394:Molecular Structure; D011898:Ranidae; D012584:Sciatic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D020927:Dexmedetomidine