title: Intravenous and intratracheal administration of trimetoquinol, a fast-acting short-lived bronchodilator in horses with 'heaves'.
abstract: BACKGROUND
  Trimetoquinol (TMQ) is a potent beta-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with 'heaves'.
  
  
  OBJECTIVE
  To assess the pharmacodynamics of TMQ in horses with 'heaves' to determine potential therapeutic effects.
  
  
  METHODS
  Increasing doses of TMQ were administered to horses with 'heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001-0.2 microg/kg bwt i.v. and 0.01-2 microg/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural pressure (deltaPplmax), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action to i.v. (0.2 microg/kg bwt) and i.t. (2 microg/kg bwt) TMQ was evaluated over 6 h.
  
  
  RESULTS
  Intravenous TMQ was an exceptionally potent cardiac stimulant. Heart rate increased at 0.01 microg/kg bwt, and was still increasing after administration of highest dose, 0.2 microg/kg bwt. Airway bronchodilation, measured as a decrease in deltaPplmax, also commenced at 0.01 microg/kg bwt. By the i.t. route, TMQ was 50-100-fold less potent than by i.v. Side effects included sweating, agitation and muscle trembling. Overall, the onset of HR and bronchodilator effects was rapid, within about 3 min, but effects were over at 2 h.
  
  
  CONCLUSIONS
  When administered i.v. and i.t., TMQ is a highly potent cardiac stimulant and a modest bronchodilator. It may not be an appropriate pharmacological agent by i.v. and i.t. routes for the alleviation of signs in horses with 'heaves'. Further studies of TMQ by oral and aerosol routes are necessary.
  
  
  CONCLUSIONS
  In horses, TMQ is a fast-acting bronchodilator with a short duration of action. It could be used as a rescue agent during an episode of 'heaves'. The i.v. and i.t. administration of TMQ is associated with side effects, similar to those reported for all other beta-agonists. However, other routes, such as aerosol and oral, may prove useful and safe for the alleviation of bronchoconstriction typical of 'heaves'.
authors.affiliation: Maxwell H. Gluck Equine Research Center, Lexington, Kentucky 40546, USA.
authors.forename: F C
authors.initials: FC
authors.lastname: Camargo
authors.forename: N E
authors.initials: NE
authors.lastname: Robinson
authors.forename: C
authors.initials: C
authors.lastname: Berney
authors.forename: S
authors.initials: S
authors.lastname: Eberhart
authors.forename: S
authors.initials: S
authors.lastname: Baker
authors.forename: P
authors.initials: P
authors.lastname: DeTolve
authors.forename: F J
authors.initials: FJ
authors.lastname: Derksen
authors.forename: J D
authors.initials: JD
authors.lastname: Harkins
authors.forename: A F
authors.initials: AF
authors.lastname: Lehner
authors.forename: T
authors.initials: T
authors.lastname: Tobin
mesh_terms: D000818:Animals; D001982:Bronchial Diseases / Q000188:drug therapy / Q000662:veterinary*; D001993:Bronchodilator Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000379:methods / Q000662:veterinary*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D007275:Injections, Intravenous / Q000009:adverse effects / Q000379:methods / Q000662:veterinary; D007442:Intubation, Intratracheal / Q000009:adverse effects / Q000379:methods / Q000662:veterinary; D008297:Male; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012449:Safety; D016896:Treatment Outcome; D014213:Tretoquinol / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D001993:Bronchodilator Agents; D014213:Tretoquinol