The Use of Dexmedetomidine Hydrochloride as a Single Pharmaceutical and in Combination with Ketamine for Sedation of Cynomolgus Macaques (Macaca fascicularis).

Sedation in nonhuman primates (NHPs) is commonly achieved with ketamine (KET), which provides short-term (less than 30 minutes) sedation but is associated with undesirable side effects such as twitching, increased jaw tone, and hypersalivation. This study investigates the use of dexmedetomidine (DEX) in cynomolgus macaques (Macaca fascicularis) as a potential alternative or adjunct sedative. Four experiments were conducted to determine: (1) the safety and efficacy of DEX as a sole sedative; (2) optimal dose combinations of DEX and KET; (3) a comparison of DEX/KET sedation outcomes to historical KET-only sedation data; and (4) a comparison of the sedation duration of DEX/KET combinations to KET alone. First, we evaluated escalating doses of DEX (0.02-4.04 mg/kg), and in 11 of 14 attempts, animals remained rousable and maintained posture for up to 90 minutes. Then, we used a fixed DEX dose (0.75 mg/kg) combined with escalating KET doses (1.0-2.252 mg/kg) to reduce overall KET exposure and successfully achieved 90 minutes of sedation. We then compared DEX/KET sedation outcomes to prior KET-only sedation records, revealing fewer instances of emesis, less food waste, and improved repairing success with DEX/KET. Finally, KET alone (10 mg/kg) or a DEX/KET combination (0.75 mg/kg DEX and 2.25 mg/kg KET) was evaluated for routine colony management procedures without atipamezole (ATI) reversal. The DEX/KET group exhibited significantly longer sedation durations with reduced hypersalivation and vomiting compared with the KET-only group. These experiments demonstrated that DEX alone was insufficient for sedation in macaques at the tested doses and had no adverse outcomes at significantly higher doses than previously reported. We recommend a DEX/KET dose of 0.75 mg/kg DEX and 2.25 mg/kg KET to provide sedation and reduce side effects (vomiting, food waste).