Clinical effects and pharmacokinetic variables of romifidine and the peripheral α2‐adrenoceptor antagonist MK‐467 in horses

The impact of MK‐467 on plasma drug concentrations, sedation and cardiopulmonary changes in sheep treated with intramuscular medetomidine and atipamezole for reversal

“…MK‐467 is a peripherally acting α 2 ‐adrenoceptor antagonist that poorly penetrates mammalian central nervous tissues; its α 2 ‐ vs. ‐α 1 selectivity ratio is approximately 105:1 (Clineschmidt et al., ). The ability of MK‐467 to attenuate the adverse haemodynamic influences attributed to α 2 ‐agonists has been reported in several species, such as dogs (Enouri, Kerr, McDonell, O'Sullivan, & Neto, ; Honkavaara, Restitutti, Raekallio, Kuusela, & Vainio, ; Pagel et al., ; Rolfe, Kerr, & McDonell, ), horses (Bryant et al., ; Vainionpää et al., ; de Vries et al., ), cats (Honkavaara, Pypendop, & Ilkiw, 2017; Pypendop, Honkavaara, & Ilkiw, ) and sheep (Bryant et al., ; Raekallio et al., ). Furthermore, MK‐467 had no substantial effect on the intensity of sedation induced by medetomidine or dexmedetomidine (Restitutti, Honkavaara, Raekallio, Kuusela, & Vainio, ; Rolfe et al., ).…”

Effects of vatinoxan on cardiorespiratory function and gastrointestinal motility during constant‐rate medetomidine infusion in standing horses

“…Thus, vatinoxan may reduce the peripheral adverse effects of α 2 ‐agonists without interfering with their centrally mediated sedative or analgesic effects. In previous equine studies, vatinoxan prevented the adverse cardiovascular effects of simultaneously administered single doses of the α 2 ‐agonists medetomidine , detomidine and romifidine . Although vatinoxan increased the volume of distribution and clearance of detomidine and romifidine in horses, it did not have clinically relevant effects on the degree of sedation.…”

Changes in energy metabolism, and levels of stress-related hormones and electrolytes in horses after intravenous administration of romifidine and the peripheral α-2 adrenoceptor antagonist vatinoxan

“…The remaining cranial jugular catheter was used for blood sampling. The arterial catheter was used for sampling for arterial blood gas analysis and for monitoring arterial blood pressure, and the central venous catheter for monitoring central venous blood pressure; these results are a subject of a separate paper [ 26 ]. The horses used in the study were research horses that were accustomed to minor procedures like IV punctures.…”

“…Vatinoxan, in addition, enhanced insulin responses to glucose in mice [ 21 ] and to exercise in humans [ 23 ]; although, in another study vatinoxan showed no effect on plasma glucose, insulin or insulin response to glucose in humans [ 24 ]. The effect of vatinoxan on quality of sedation induced by detomidine or romifidine in horses [ 25 , 26 ] and dexmedetomidine in dogs [ 27 – 29 ] is only minor because it acts predominantly on peripheral α-2 adrenoceptors.…”