title: Effects of adrenergic agonists and antagonists on tetrodotoxin-induced nerve block.
abstract: OBJECTIVE
  The relative contributions of alpha(1)-, alpha(2)-, and beta-adrenergic receptors to adrenergic agonists' prolongation of nerve block by tetrodotoxin (TTX) are unknown. We investigated which receptor agonists prolong TTX block, and whether delayed injection of antagonists can interrupt prolonged blocks after coinjection of TTX and agonists.
  
  
  METHODS
  Rats received percutaneous sciatic nerve block with 120 micromol/L TTX with and without adrenergic agonists and antagonists. Block duration was assessed by a modified hot-plate test. Functional deficits in the uninjected leg were used to assess systemic distribution of TTX. Data were expressed as medians with 25th and 75th percentiles.
  
  
  RESULTS
  Coinjection of 5.5 micromol/L phenylephrine (alpha(1)-specific), 10 micromol/L clonidine (alpha(2)-specific), and 1.1 micromol/L epinephrine (mixed alpha- and beta-agonist) prolonged TTX nerve block, but 5.5 micromol/L isoproterenol (mixed beta-agonist) did not. Yohimbine inhibited TTX block prolongation by clonidine (median inhibitory concentrations, IC(50) = 130 nmol/L); phentolamine similarly inhibited epinephrine (IC(50) = 45 nmol/L). Adrenergic antagonists did not inhibit the prolongation of TTX block by agonists when injected 3 or 6 hours after the initial block. Subcutaneous injection of adrenergic agonists at a remote site did not prolong TTX block, except for a modest prolongation by clonidine.
  
  
  CONCLUSIONS
  TTX block can be prolonged by alpha(1)- and alpha(2)-, but not beta-adrenergic agonists via locally mediated events of relatively brief duration. Delayed injection of adrenergic antagonists does not interrupt the prolonged blocks produced by coinjection of TTX and adrenergic agonists unless administered soon after block is established. Reg Anesth Pain Med 2001;26:239-245.
authors.affiliation: Department of Anesthesia, Children's Hospital, Pain Treatment Service, 333 Longwood Ave., Boston, MA 02115, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Kohane
authors.forename: N T
authors.initials: NT
authors.lastname: Lu
authors.forename: B E
authors.initials: BE
authors.lastname: Cairns
authors.forename: C B
authors.initials: CB
authors.lastname: Berde
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology*; D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009407:Nerve Block; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D013997:Time Factors
chemical_list: D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D026941:Sodium Channel Blockers; D010656:Phenylephrine; D013779:Tetrodotoxin; D007545:Isoproterenol; D003000:Clonidine; D004837:Epinephrine; D010646:Phentolamine