Evaluating the Physiological and Sedation Parameters of Zenalpha (Medetomidine and Vatinoxan Hydrochloride Injection) in Combination with Ketamine in Rhesus Macaques (Macaca mulatta)

Alpha-2 adrenergic agonists such as dexmedetomidine are widely used for sedation in rhesus macaques (Macaca mulatta) but are associated with undesired cardiovascular effects. Zenalpha (Dechra, Overland Park, KS), a combination of medetomidine and the peripheral α2 antagonist vatinoxan, has demonstrated improved physiologic stability in other species but has not been evaluated in nonhuman primates. This study assessed the cardiopulmonary effects and sedation quality of ketamine alone, ketamine combined with dexmedetomidine (500 μg/m2) for 30 or 60 minutes, and ketamine combined with Zenalpha (medetomidine 1 mg/m2 and vatinoxan 20 mg/m2) for 30 or 60 minutes in 10 adult rhesus macaques with 7-day washout intervals between immobilization events. A second study phase evaluated reduced α2 agonist doses, with each animal undergoing 2 additional immobilization events: ketamine + dexmedetomidine (250 μg/m2) and ketamine + Zenalpha (0.5 mg/m2). Physiologic parameters were recorded every 5 minutes, and sedation depth was scored every 10 minutes. Atipamezole (5,000 μg/m2 IM) was administered after the assigned immobilization period for dexmedetomidine and Zenalpha sessions (30 or 60 minutes). Across both phases, ketamine + Zenalpha produced higher heart rates, higher oxygen saturation, and lower mean arterial pressure compared with ketamine + dexmedetomidine while maintaining adequate sedation for up to 60 minutes. Reduced-dose protocols in phase 2 produced sedation comparable to full-dose combinations. These findings suggest that Zenalpha combined with ketamine may offer a more balanced cardiovascular profile than dexmedetomidine-based sedation protocols in rhesus macaques.