​Medetomidine is a sedative drug that is widely used for anesthesia in various animals. Its effects can be reversed by an antagonist, allowing us to easily control the duration of sedation. However, medetomidine has cardiovascular side effects, such as bradycardia or arrhythmia. These adverse effects are a major concern in various animal species. Recently, there have been reports of cardiac diseases in macaques, which underscores the necessity for safer anesthesia with reduced cardiovascular side effects. Therefore, we focused on vatinoxan, a peripheral α2-adrenoceptor antagonist. This drug is expected to reduce the cardiovascular side effects associated with medetomidine by reversing its effects only at the peripheral level while maintaining its central sedative effects. 
Currently, a combination product containing medetomidine and vatinoxan is commercially available for dogs under the name “Zenalpha”.
At the Institute for the Evolutionary Origins of Human Behavior, Kyoto University (EHUB), we have used a balanced anesthetic protocol, the medetomidine-midazolam-ketamine (MMK) protocol, in two macaque species: Japanese macaques and rhesus macaques. In this study, we compared the Zenalpha-midazolam-ketamine (ZMK) and MMK protocols to evaluate their cardiovascular effect. The results showed that Zenalpha can reduce bradycardia and valve regurgitation while maintaining sedative effects comparable to those of MMK. These findings are expected to contribute to the development of safer anesthetic management in macaques
This study was published in the Journal of Medical Primatology on May 14, 2026.