Investigation of the effects of vatinoxan on somatic and visceral antinociceptive efficacy of medetomidine in dogs

Abstract

OBJECTIVETo determine whether concurrent vatinoxan administration affects the antinociceptive efficacy of medetomidine in dogs at doses that provide circulating dexmedetomidine concentrations similar to those produced by medetomidine alone. ANIMALS 8 healthy Beagles. PROCEDURESDogs received 3 IV treatments in a randomized crossover-design trial with a 2-week washout period between experiments (medetomidine [20 µg/ kg], medetomidine [20 µg/kg] and vatinoxan [400 µg/kg], and medetomidine [40 µg/kg] and vatinoxan [800 µg/kg]; M20, M20V400, and M40V800, respectively). Sedation, visceral and somatic nociception, and plasma drug concentrations were assessed. Somatic and visceral nociception measurements and sedation scores were compared among treatments and over time. Sedation, visceral antinociception, and somatic antinociception effects of M20V400 and M40V800 were analyzed for noninferiority to effects of M20, and plasma drug concentration data were assessed for equivalence between treatments. RESULTSPlasma dexmedetomidine concentrations after administration of M20 and M40V800 were equivalent. Sedation scores, visceral nociception measurements, and somatic nociception measurements did not differ significantly among treatments within time points. Overall sedative effects of M20V400 and M40V800 and visceral antinociceptive effects of M40V800 were noninferior to those produced by M20. Somatic antinociception effects of M20V400 at 10 minutes and M40V800 at 10 and 55 minutes after injection were noninferior to those produced by M20. CONCLUSIONS AND CLINICAL RELEVANCEResults suggested coadministration with vatinoxan did not substantially diminish visceral antinociceptive effects of medetomidine when plasma dexmedetomidine concentrations were equivalent to those produced by medetomidine alone. For somatic antinociception, noninferiority of treatments was detected at some time points.

Various Systemic Effects of MK-467, A Peripherally Acting α2-adrenoceptor Antagonist in Different Animal Species: An Overview

“…Effects of dexmedetomidine, with or without vatinoxan, on the minimum alveolar concentration of isoflurane (MAC) in cats, have been investigated by Pypendop et al (2019a) and they advocated that vatinoxan increases the MAC of isoflurane in cats along with diminishing the potency of dexmedetomidine in reducing MAC. Huuskonen et al (2020) researched concerning the effect of simultaneous administration of vatinoxan on the antinociceptive efficacy of medetomidine in dogs, at doses providing circulating dexmedetomidine concentration equivalent to those produced by medetomidine alone. This randomized crossover study was performed in eight healthy beagle dogs, each receiving 3 intravenous treatment: medetomidine (20 μg/kg), medetomidine (20 μg/kg) with vatinoxan (400 μg/kg) and medetomidine (40 μg/kg) with vatinoxan (800 μg/kg), respectively and the sedation score, visceral and somatic nociception and the plasma drug concentration were assessed.…”

Effects of vatinoxan on xylazine‐induced pulmonary alterations in sheep

“…This concept has been well‐documented in various species (Honkavaara et al, 2011; Restitutti et al, 2012; Rolfe et al, 2012; Sainmaa et al, 2019; Siao et al, 2017; de Vires et al, 2016), including sheep (Adam, Huuskonen, et al, 2018; Adam, Raekallio, Keskitalo, et al, 2018; Adam, Raekallio, Salla, et al, 2018; Bryant et al, 1998; Raekallio et al, 2010). Moreover, vatinoxan has no appreciable impact on agonist‐induced sedation in many species (Adam, Raekallio, Keskitalo, et al, 2018; Adam, Raekallio, Salla, et al, 2018; Honkavaara Pypendop et al, 2017; Honkavaara et al, 2008, 2017; Raekallio et al, 2010; Restitutti et al, 2011; Siao et al, 2017; Tapio et al, 2018; Vainionpää et al, 2013; de Vries et al, 2016), nor has it shown antinociceptive effects when the agonist concentration is similar in plasma (Huuskonen et al, 2020). Recently, we demonstrated in sheep that premedication with vatinoxan alleviated dexmedetomidine‐induced bronchoconstriction and hypoxaemia, and prevented the opacity detected by computer tomography (CT) in the ventrolateral parts of lungs (Adam, Huuskonen, et al, 2018).…”