Alpha‐2‐adrenoreceptor agonists as analgesic drugs in equine medicine

Summary Managing pain in horses is challenging despite the availability of nonsteroidal anti‐inflammatory drugs, local anaesthetics, opioids and α 2 ‐adrenoreceptor agonists. While α 2 ‐agonists are widely used for sedation and restraint, their analgesic properties remain underutilised. This review outlines their mechanisms, clinical applications and limitations in equine practice. Commonly used agents, including xylazine, detomidine, romifidine, medetomidine and dexmedetomidine, act on α 2 ‐adrenoreceptor subtypes in the central and peripheral nervous system. Centrally, they reduce norepinephrine release and nociceptive transmission, producing sedation and analgesia. Peripherally, they cause transient vasoconstriction, decreased gastrointestinal motility, hyperglycaemia and diuresis. Cardiovascular effects typically follow a biphasic pattern of hypertension and bradycardia, then hypotension. Clinically, α 2 ‐agonists are integral for managing colic pain, reducing inhalant anaesthetic requirements and providing multimodal analgesia. They can be administered intravenously, intramuscularly, epidurally or transmucosally, with epidural use producing prolonged effects when combined with local anaesthetics. Xylazine and dexmedetomidine act rapidly but briefly, whereas detomidine and romifidine provide longer sedation and analgesia. Reversal agents such as yohimbine, tolazoline and atipamezole exist, though side effects limit routine use. Their use may be limited by regulatory and licensing restrictions, potential for human abuse and adverse effects such as dysphoria and gastrointestinal stasis. Vatinoxan, a peripherally selective antagonist, may allow sedation with reduced cardiovascular depression while preserving central sedative and analgesic effects. A persistent challenge is separating analgesia from sedation, as both overlap clinically. Evidence suggests that analgesic duration varies by drug, and future research should aim to develop α 2 ‐agonists with potent analgesic but minimal sedative effects to improve equine pain management.