title: Dexmedetomidine and clonidine induce long-lasting activation of the respiratory rhythm generator of neonatal mice: possible implication for critical care.
abstract: Dexmedetomidine and clonidine are alpha-2 adrenoceptor agonists increasingly used in the critical care unit as sedative agents for their benzodiazepine-sparing effects and their limited depressing effect on breathing. However adverse effects on breathing have been also reported with alpha-2 adrenoceptor agonists and their central effects on the respiratory rhythm generator are poorly known. We therefore examined the effects of dexmedetomidine, clonidine, the alpha-2 adrenoceptor antagonist yohimbine and the benzodiazepine midazolam on the activity of the isolated respiratory rhythm generator of neonatal mice using medullary preparations where the respiratory rhythm generator continued to function in vitro. For the first time, we showed that 5min bath applications of dexmedetomidine or clonidine activated the respiratory rhythm generator for periods over than 30min. Second, we showed that the long-lasting effect of dexmedetomidine implicated receptors other than alpha-2 adrenoceptors as it persisted after their blockade with yohimbine. Third, we reported that 5min bath applications of the benzodiazepine midazolam significantly depressed the respiratory rhythm generator, and that this depression was prevented by pre-treatment with either dexmedetomidine or clonidine. Although further experiments are still required to identify the mechanisms through which dexmedetomidine and clonidine activate the respiratory rhythm generator, our current in vitro results in neonatal mice support the use of dexmedetomidine and clonidine in the critical care unit.
authors: Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, Unité Mixte de Recherche 6231 Centre National Recherche Scientifique/Université Aix-Marseille II et III, Team mp3-Respiration, Faculté Saint-Jérôme (case 362), 13397 Marseille Cedex 20, France.
authors: Nicolas
authors: N
authors: Voituron
authors: Gérard
authors: G
authors: Hilaire
authors: Luc
authors: L
authors: Quintin
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D003000:Clonidine / Q000494:pharmacology*; D020927:Dexmedetomidine / Q000494:pharmacology*; D051379:Mice; D012119:Respiration / Q000187:drug effects*; D012125:Respiratory Center / Q000187:drug effects* / Q000502:physiology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D020927:Dexmedetomidine; D003000:Clonidine