Abstract: Myocardial ischemia/reperfusion injury (MI/RI) is a common complication of coronary artery recanalization after myocardial infarction, which seriously affects the recovery of patients and even threatens their life. Opioids can not only provide analgesia, but also protect the heart, which depends on the activation of opioid receptor (OR). The activation of κ‑OR and δ‑OR is directly involved in myocardial protection, while the role and mechanism of μ‑OR remain controversial. In addition, the affinity of different agonists to three OR subtypes makes the conclusion "OR mediated cardiac protection" controversial. This paper reviews the protective effects of endogenous opioid peptides and exogenous opioids such as morphine, fentanyl, remifentanil, butorphanol and methadone on MI/RI. At the same time, we will further discuss the mechanisms of different opioid receptors mediated cardioprotection, their crosstalk with other members of the G protein‑coupled receptor (GPCR) family, and possible upstream and downstream signaling pathways to provide enlightenment for development of drugs in the future.
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