RB101-mediated Protection of Endogenous Opioids: Potential Therapeutic Utility?

Emily M. Jutkiewicz
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引用次数: 24

Abstract

The endogenous opioids met- and leu-enkephalin are inactivated by peptidases preventing the activation of opioid receptors. Inhibition of enkephalin-degrading enzymes increases endogenous enkephalin levels and stimulates robust behavioral effects. RB101, an inhibitor of enkephalin-degrading enzymes, produces antinociceptive, antidepressant, and anxiolytic effects in rodents, without typical opioid-related negative side effects. Although enkephalins are not selective endogenous ligands, RB101 induces these behaviors through receptor-selective activity. The antinociceptive effects of RB101 are produced through either the mu-opioid receptor alone or through activation of both mu- and delta-opioid receptors; the antidepressant-like and anxiolytic effects of RB101 are mediated only through the delta-opioid receptor. Although little is known about the effects of RB101 on other physiologically and behaviorally relevant peptides, these findings suggest that RB101 and other inhibitors of enkephalin-degrading enzymes may have potential as novel therapeutic compounds for the treatment of pain, depression, and anxiety.

Abstract Image

rb101介导的内源性阿片类药物保护:潜在的治疗用途?
内源性阿片类物质乙酰脑啡肽和左脑啡肽被肽酶灭活,阻止了阿片类受体的激活。抑制脑啡肽降解酶可增加内源性脑啡肽水平并刺激强健的行为效应。RB101是一种脑啡肽降解酶的抑制剂,在啮齿类动物中产生抗痛觉、抗抑郁和抗焦虑作用,没有典型的阿片类药物相关的负面副作用。虽然脑啡肽不是选择性内源性配体,但RB101通过受体选择性活性诱导这些行为。RB101的抗感觉作用是通过单独的阿片受体或通过激活阿片受体和阿片受体产生的;RB101的抗抑郁和抗焦虑作用仅通过阿片受体介导。尽管RB101对其他生理和行为相关肽的作用知之甚少,但这些发现表明,RB101和其他脑啡肽降解酶抑制剂可能有潜力成为治疗疼痛、抑郁和焦虑的新型治疗化合物。
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