Respiratory depression is a potentially fatal side effect of opioid analgesics and major limitation to their use. G-protein-biased opioid agonists have been proposed as "safer" analgesics with less respiratory depression. These agonists are biased to activate G proteins rather than β-arrestin signaling. Respiratory depression has been shown to correlate with both G-protein bias and intrinsic efficacy, and recent work has refuted the role of β-arrestin signaling in opioid-induced respiratory depression. In addition, there is substantial evidence that G-proteins do, in fact, mediate respiratory depression by actions in respiratory-controlling brainstem neurons. Based on these studies, we provide the perspective that protection from respiratory depression displayed by newly developed G-protein biased agonists is due to factors other than G-protein versus arrestin bias.

中文翻译：

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评估阿片类药物诱导的呼吸抑制中的 G 蛋白偏倚和 β-arrestin 2 信号传导。

呼吸抑制是阿片类镇痛剂的潜在致命副作用，也是对其使用的主要限制。G 蛋白偏向的阿片样物质激动剂已被提议作为“更安全”的镇痛剂，呼吸抑制较少。这些激动剂偏向于激活 G 蛋白而不是 β-arrestin 信号。呼吸抑制已被证明与 G 蛋白偏倚和内在功效相关，最近的工作驳斥了 β-arrestin 信号传导在阿片类药物诱导的呼吸抑制中的作用。此外，有大量证据表明 G 蛋白实际上通过控制呼吸的脑干神经元中的作用介导呼吸抑制。基于这些研究，