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 α2-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 μg kg⁻¹ IV, DEX) alone or in combination with L-659,066 (250 μg 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 μg 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 α2-adrenoceptor agonists could be markedly improved with less peripheral cardiovascular effects.