title: The alpha 2-adrenergic agonists clonidine and guanfacine produce tonic and phasic block of conduction in rat sciatic nerve fibers.
abstract: To determine whether alpha 2-adrenergic agonists inhibit impulse conduction, clonidine and guanfacine were applied to rat sciatic nerve fibers studied in vitro. Clonidine and guanfacine produced concentration-dependent, tonic inhibition of compound action potentials in large, myelinated A alpha fibers. The 50% effective concentration (EC50) of clonidine measured 2.0 +/- 0.8 mM (mean +/- standard deviation); the EC50 of guanfacine measured 1.2 +/- 0.2 mM. Clonidine was also less potent than guanfacine at phasic block of A alpha compound action potentials examined at 10 Hz. Both drugs inhibited tonic impulse conduction in C fibers in a concentration-dependent, reversible fashion, and produced greater inhibition of C fiber than A alpha compound action potentials at all drug concentrations. Again, clonidine appeared to inhibit C fiber compound action potentials (EC50 = 0.45 +/- 0.01 mM) with less potency than guanfacine (EC50 = 0.17 +/- 0.06 mM). We conclude that clonidine and guanfacine, unlike traditional local anesthetics, demonstrate a tendency toward steady-state differential nerve block wherein C fibers are blocked to a greater extent than A alpha fibers.
authors.affiliation: Department of Anesthesia, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1009.
authors.forename: J F
authors.initials: JF
authors.lastname: Butterworth
authors.forename: G R
authors.initials: GR
authors.lastname: Strichartz
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016316:Guanfacine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009407:Nerve Block; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects* / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D016316:Guanfacine; D003000:Clonidine