title: Effects of different doses of L-659'066 on the bispectral index and clinical sedation in dogs treated with dexmedetomidine.
abstract: OBJECTIVE
  To evaluate the effects of three doses of L-659'066 (MK-467) on the bispectral index (BIS) and clinical sedation in dexmedetomidine-sedated Beagles.
  
  
  METHODS
  Randomized, experimental cross over study.
  
  
  METHODS
  Eight purpose-bred healthy laboratory Beagles.
  
  
  METHODS
  Dexmedetomidine (10 μg kg(-1) IV [DEX]) was administered alone or in combination with three doses of L-659'066 (250 μg kg(-1) [DL250]; 500 μg kg(-1) [DL500] and 750 μg kg(-1) [DL750] IV) in the same syringe in a randomized crossover manner. The bispectral index (BIS), electromyography (EMG) and sedation score were recorded at baseline and 5, 10, 20, 30, 45 and 60 minutes after treatment.
  
  
  RESULTS
  When compared to DEX, BIS and EMG were significantly higher and the sedation score significantly lower with DL500 and DL750. With DEX, BIS was significantly decreased at times 20, 30 and 60 minutes whereas the sedation scores were significantly increased at all time points after drug administration in all groups. Bioequivalence for clinical sedation was detected between DEX and all doses of L-659'066, reaching European Medicines Agency (EMA) standards.
  
  
  CONCLUSIONS
  Although L-659'066 interfered with dexmedetomidine induced sedation, the degree of the reduction was not clinically relevant. Despite performing better when dexmedetomidine was used alone, BIS did not reflect the clinical sedative status when the antagonist was added.
authors.affiliation: Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland. flavia.restitutti@helsinki.fi
authors.forename: Flavia
authors.initials: F
authors.lastname: Restitutti
authors.forename: Juhana M
authors.initials: JM
authors.lastname: Honkavaara
authors.forename: Marja R
authors.initials: MR
authors.lastname: Raekallio
authors.forename: Erja K
authors.initials: EK
authors.lastname: Kuusela
authors.forename: Outi M
authors.initials: OM
authors.lastname: Vainio
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D016292:Procedural Sedation / Q000662:veterinary*; D056805:Consciousness Monitors / Q000662:veterinary*; D020927:Dexmedetomidine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004576:Electromyography / Q000662:veterinary; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D011807:Quinolizines / Q000494:pharmacology*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D006993:Hypnotics and Sedatives; D011807:Quinolizines; C055732:vatinoxan; D020927:Dexmedetomidine