title: Effects of three antagonists on selected pharmacodynamic effects of sublingually administered detomidine in the horse.
abstract: OBJECTIVE
  To describe the effects of alpha2 -adrenergic receptor antagonists on the pharmacodynamics of sublingual (SL) detomidine in the horse.
  
  
  METHODS
  Randomized crossover design.
  
  
  METHODS
  Nine healthy adult horses with an average age of 7.6 ± 6.5 years.
  
  
  METHODS
  Four treatment groups were studied: 1) 0.04 mg kg(-1) detomidine SL; 2) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.075 mg kg(-1) yohimbine intravenously (IV); 3) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 4 mg kg(-1) tolazoline IV; and 4) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.12 mg kg(-1) atipamezole IV. Each horse received all treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for yohimbine, atipamezole and tolazoline concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume (PCV) and plasma proteins were monitored.
  
  
  RESULTS
  Chin-to-ground distance increased following administration of the antagonists, however, this effect was transient, with a return to pre-reversal values as early as 1 hour. Detomidine induced bradycardia and increased incidence of atrioventricular blocks were either transiently or incompletely antagonized by all antagonists. PCV and glucose concentrations increased with tolazoline administration, and atipamezole subjectively increased urination frequency but not volume.
  
  
  CONCLUSIONS
  At the doses administered in this study, the alpha2 -adrenergic antagonistic effects of tolazoline, yohimbine and atipamezole on cardiac and behavioral effects elicited by SL administration of detomidine are transient and incomplete.
authors.affiliation: K. L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA; Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: Heather K
authors.initials: HK
authors.lastname: Knych
authors.forename: Scott D
authors.initials: SD
authors.lastname: Stanley
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006736:Horses / Q000097:blood*; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D014043:Tolazoline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D015016:Yohimbine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole; D015016:Yohimbine; C041255:detomidine; D014043:Tolazoline
keywords: alpha2-adrenergic agonist; antagonist; atipa-mezole; detomidine; equine; tolazoline; yohimbine