The effects of L-659,066, a peripheral alpha2-adrenoceptor antagonist, on dexmedetomidine-induced sedation and bradycardia in dogs.
OBJECTIVE
To investigate the influence of L-659,066, a peripheral alpha2-adrenoceptor antagonist, on dexmedetomidine-induced sedation and reduction in pulse rate (PR) in dogs.


METHODS
Randomized, cross-over. Animals Six healthy laboratory Beagles.


METHODS
All animals received dexmedetomidine (5 microg kg(-1) IV, DEX) alone or in combination with L-659,066 (250 microg kg(-1) IV, DEX + L) with a 7-day rest period between treatments. Sedation was assessed using a composite sedation score and PRs were recorded. Atipamezole (50 microg kg(-1) IM, ATI) was administered to reverse the sedation. Overnight Holter-monitoring was carried out to obtain a minimum heart rate (MHR) at rest.


RESULTS
Bioequivalence was shown for clinical sedation between DEX and DEX + L. Heart rate was significantly higher with DEX + L during the period of sedation. Bioequivalence was demonstrated between MHR and PR in the DEX + L group during the period of sedation. Recoveries after ATI were uneventful.


CONCLUSIONS
L-659,066 did not affect the quality of dexmedetomidine-induced sedation whilst it attenuated the reduction in PR. Thus, L-659,066 could prove a useful adjunct to reduce the peripheral cardiovascular effects attributed to dexmedetomidine in dogs.


CONCLUSIONS
The clinical safety of alpha2-adrenoceptor agonists could be markedly improved with less peripheral cardiovascular effects.
Honkavaara
Juhana M
JM
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Finland. jussi.honkavaara@helsinki.fi
Raekallio
Marja R
MR
Kuusela
Erja K
EK
Hyvärinen
Esko A
EA
Vainio
Outi M
OM
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000758:Anesthesia / Q000009:adverse effects / Q000662:veterinary; D000818:Animals; D001919:Bradycardia / Q000139:chemically induced / Q000188:drug therapy / Q000662:veterinary*; D018592:Cross-Over Studies; D020927:Dexmedetomidine / Q000494:pharmacology*; D004283:Dog Diseases / Q000139:chemically induced*; D004285:Dogs; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D011807:Quinolizines / Q000494:pharmacology*
D018674:Adrenergic Antagonists; D006993:Hypnotics and Sedatives; D011807:Quinolizines; C055732:vatinoxan; D020927:Dexmedetomidine