Hyperactivity in Mice Induced by Opioid Agonists with Partial Intrinsic Efficacy and Biased Agonism Administered Alone and in Combination with Morphine.
Hyperactivity in Mice Induced by Opioid Agonists with Partial Intrinsic Efficacy and Biased Agonism Administered Alone and in Combination with Morphine.
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DOI：
10.3390/biom13060935
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发表时间：
2023-06-02
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
阿片类镇痛药如吗啡和芬太尼诱导小鼠μ阿片受体（莫尔）介导的活动过度。在此，我们使用35 S-GTP γS结合试验表明吗啡、芬太尼、SR-17018和oliceridine在小鼠纹状体中具有次最大的内在功效。虽然所有的激动剂作为刺激纹状体G蛋白偶联的部分激动剂，吗啡，芬太尼，和oliceridine是完全有效的刺激自发活动，同时，非竞争性偏激动剂SR-17018和SR-15099产生次最大的活动过度。此外，SR-17018和吗啡的组合减弱了多动症，同时增加了抗伤害性功效。oliceridine与吗啡联合使用会增加多动症，并随着时间的推移而维持。这些发现提供了证据表明，在莫尔的非竞争性激动剂可用于抑制吗啡诱导的多动症，同时提高抗伤害性功效，此外，他们证明，在受体水平上测量的内在功效是不直接成比例的药物功效的自发活动测定。
Opioid analgesics such as morphine and fentanyl induce mu-opioid receptor (MOR)-mediated hyperactivity in mice. Herein, we show that morphine, fentanyl, SR-17018, and oliceridine have submaximal intrinsic efficacy in the mouse striatum using 35S-GTPγS binding assays. While all of the agonists act as partial agonists for stimulating G protein coupling in striatum, morphine, fentanyl, and oliceridine are fully efficacious in stimulating locomotor activity; meanwhile, the noncompetitive biased agonists SR-17018 and SR-15099 produce submaximal hyperactivity. Moreover, the combination of SR-17018 and morphine attenuates hyperactivity while antinociceptive efficacy is increased. The combination of oliceridine with morphine increases hyperactivity, which is maintained over time. These findings provide evidence that noncompetitive agonists at MOR can be used to suppress morphine-induced hyperactivity while enhancing antinociceptive efficacy; moreover, they demonstrate that intrinsic efficacy measured at the receptor level is not directly proportional to drug efficacy in the locomotor activity assay.
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影响因子：
2.5
作者：
Hall, FS;Li, XF;Uhl, GR
通讯作者：
Uhl, GR
影响因子：
64.5
作者：
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影响因子：
56.9
作者：
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通讯作者：
Lin, FT
影响因子：
7.6
作者：
Sora, I;Elmer, G;Uhl, GR
通讯作者：
Uhl, GR
影响因子：
5.4
作者：
Kudla L;Bugno R;Podlewska S;Szumiec L;Wiktorowska L;Bojarski AJ;Przewlocki R
通讯作者：
Przewlocki R