Peripherally acting α-adrenoceptor antagonist MK-467 with intramuscular medetomidine and butorphanol in dogs: A prospective, randomised, clinical trial.

Kallio-Kujala, I J; Turunen, H A; Raekallio, M R; Honkavaara, J M; Salla, K M; Casoni, Daniela; Hautajärvi, H J; Vainio, O M (2018). Peripherally acting α-adrenoceptor antagonist MK-467 with intramuscular medetomidine and butorphanol in dogs: A prospective, randomised, clinical trial. Veterinary journal, 240, pp. 22-26. Elsevier 10.1016/j.tvjl.2018.08.007

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The aim of this study was to investigate the clinical usefulness of MK-467 (vatinoxan; L-659'066) in dogs sedated for diagnostic imaging with medetomidine-butorphanol. It was hypothesised that MK-467 would alleviate bradycardia, hasten drug absorption and thus intensify the early-stage sedation. In a prospective, randomised, blinded clinical trial, 56 client-owned dogs received one of two IM treatments: (1) 0.5mg/m medetomidine+0.1mg/kg butorphanol (MB, n=29); or (2) 0.5mg/m medetomidine+0.1mg/kg butorphanol+10mg/m MK-467 (MB-MK, n=27). Heart rates and visual sedation scores were recorded at intervals. Plasma drug concentrations were determined in venous samples obtained approximately 14min after injection. Additional sedation (50% of original dose of medetomidine IM) and/or IM atipamezole for reversal were given when needed. The area under the sedation score-time curve for visual analogue scale (AUC) was calculated for the first 30min after treatment using the trapezoidal method. Repeated ANOVA, Mann-Whitney U test and Fisher's exact test were used for parametric, non-parametric and dichotomous data. Heart rate was significantly higher from 10 to 40min with MB-MK than with MB. AUC was significantly higher after MB-MK. More dogs treated with MB-MK required additional sedation after 30min, but fewer needed atipamezole for reversal compared with MB. Plasma concentrations of both medetomidine and butorphanol were higher after MB-MK. All procedures were successfully completed. MK-467 alleviated the bradycardia, intensified the early stage sedation and shortened its duration in healthy dogs that received IM medetomidine-butorphanol.

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