| Summary: | Prescription opioids, such as morphine, remain an important part in the management of pain. However, their clinical utility can be limited by side effects such as constipation, nausea, and high risk of addiction. Additionally, abuse of prescription opioids has been on the rise in recent years. Therefore, it is necessary to develop effective analgesics that lack the rewarding properties of currently used opioids. The neurokinin-1 receptor (NK-1) and its endogenous ligand, Substance P (SP), have been implicated in the control of nausea and vomiting, as well as mediating the rewarding effects of opioids. Here we have characterized the side effects of a novel efficacious opioid agonist/NK-1 antagonist, TY027. TY027 fails to elicit conditioned place preference, retching or vomiting, and does not inhibit gastric motility. These findings suggest that TY027 has a superior side effect profile when compared to currently used opioids, and most importantly, it does not produce rewarding effects that may lead to addiction.
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