Abstract:
BACKGROUND AND PURPOSE: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. 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 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 AND IMPLICATIONS: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.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kosugi T,Mizuta K,Fujita T,Nakashima M,Kumamoto Edoi
10.1111/j.1476-5381.2010.00833.xsubject
Has Abstractpub_date
2010-08-01 00:00:00pages
1662-76issue
7eissn
0007-1188issn
1476-5381pii
BPH833journal_volume
160pub_type
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