Sedative effect of intramuscular medetomidine with and without vatinoxan (MK-467), and its reversal with atipamezole in sheep

Abstract Objective To evaluate the effect of the peripherally acting α 2 -adrenoceptor antagonist vatinoxan (MK-467) on the sedative properties of medetomidine (MED) when injected intramuscularly (IM) in the same syringe and on reversal of this sedation with atipamezole in sheep. Study design Randomized, blinded, crossover experimental trial. Animals Eight healthy adult female sheep. Methods Sheep received MED (30 μg kg –1 IM) alone or combined in the same syringe with vatinoxan (300 μg kg –1 IM, MED+VAT) with a 2 week washout period. Atipamezole (150 μg kg –1 IM) was administered 30 minutes later for reversal. Sedation was assessed using two sedation scores, a visual analog score and a descriptive scale before treatments (T0) and at intervals up to 5 hours thereafter. Pulse rate (PR) was counted at T0 and at 30 (T30) and 90 (T90) minutes. Rectal temperature was measured at T0 and T90 postinjection. Plasma samples were analyzed for drug concentrations at T30 and T90. Results The first signs of sedation were seen significantly earlier after MED+VAT (4.6 ± 1.7 minutes versus 9.4 ± 2.6 minutes after MED) and the sedation scores were significantly higher after MED+VAT than MED. All animals laid with head down 10.0 ± 3.4 minutes after MED+VAT, whereas three MED animals did not become recumbent before atipamezole was administered. The plasma concentrations of dexmedetomidine were significantly higher at T30 (2.47 ± 0.2 ng mL –1 ) and significantly lower at T90 (1.23 ± 0.3 ng mL –1 ) with MED+VAT than with MED (1.19 ± 0.8 and 1.83 ± 0.4 ng mL –1 , respectively). While no significant differences were observed between treatments in PR at T30, PR at T90 was significantly higher with MED+VAT than with MED. Conclusions and clinical relevance When administered IM in the same syringe, vatinoxan hastened and intensified the initial sedative effects of MED and enhanced the sedation reversal by atipamezole.