The effects of L-659,066, a peripheral alpha2-adrenoceptor antagonist, on dexmedetomidine-induced sedation and bradycardia in dogs

Abstract

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.

Study design: 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.

Clinical relevance: The clinical safety of alpha2-adrenoceptor agonists could be markedly improved with less peripheral cardiovascular effects.