Vatinoxan: a new development in the clinical use of α2-adrenoceptor agonists in dogs, part 1

Abstract

Vatinoxan, formerly known as MK-467 or L-659 066, is a peripherally acting α2 adrenoceptor antagonist. In a similar manner to atipamezole, it antagonises the pharmacodynamic effects of the α2 adrenoceptor agonist medetomidine and its active enantiomer dexmedetomidine. However, unlike atipamezole it has limited ability to penetrate the blood–brain barrier, owing to its relatively low lipid solubility. Medetomidine is an α2 adrenoceptor agonist, which is commonly used in dogs because it is a profound and consistent sedative. However, its use is also associated with many side effects, most notably those affecting the cardiovascular system, which include but are not limited to vasoconstriction, hypertension and bradycardia. When vatinoxan is co-administered intravenously with medetomidine or dexmedetomidine, it has minimal impact on the quality of sedation but vatinoxan attenuates the cardiovascular effects of medetomidine and dexmedetomidine. By ameliorating the cardiovascular effects of the agonist drugs, vatinoxan alters their pharmacokinetics, thereby shortening their duration of effect. Following intramuscular injection, vatinoxan hastens the onset of sedation and its use is associated with a greater level but a shorter duration of sedation. Therefore, vatinoxan may offer some clinically beneficial effects when it is part of a sedative drug combination or when used for premedication before general anaesthesia in dogs.