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Superior analgesic effect of H-Dmt-D-Arg-Phe-Lys-NH2 ([Dmt1]DALDA), a multifunctional opioid peptide, compared to morphine in a rat model of neuropathic pain.在神经病理性疼痛的大鼠模型中，多功能阿片肽 H-Dmt-D-Arg-Phe-Lys-NH2([Dmt1]DALDA)的镇痛效果优于吗啡。
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Increased sensitivity to acute and persistent pain in neuron-specific endothelin-1 knockout mice.神经元特异性内皮素-1基因敲除小鼠对急性和持续性疼痛的敏感性增加。
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2
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J Biol Chem. 2004 Aug 13;279(33):34682-90. doi: 10.1074/jbc.M402999200. Epub 2004 Jun 2.
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J Pharmacol Exp Ther. 2002 Jul;302(1):188-96. doi: 10.1124/jpet.302.1.188.
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Animal models of nociception.伤害感受的动物模型。
Pharmacol Rev. 2001 Dec;53(4):597-652.
6
Antinociceptive and respiratory effects of intrathecal H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA) and [Dmt1] DALDA.鞘内注射H-Tyr-D-Arg-Phe-Lys-NH2（DALDA）和[Dmt1]DALDA的抗伤害感受及呼吸效应
J Pharmacol Exp Ther. 2001 Apr;297(1):364-71.
7
Synthesis and in vitro opioid activity profiles of DALDA analogues.DALDA类似物的合成及体外阿片样物质活性谱
Eur J Med Chem. 2000 Oct;35(10):895-901. doi: 10.1016/s0223-5234(00)01171-5.
8
Opiate receptor knockout mice define mu receptor roles in endogenous nociceptive responses and morphine-induced analgesia.阿片受体基因敲除小鼠确定了μ受体在内源性伤害性反应和吗啡诱导镇痛中的作用。
Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1544-9. doi: 10.1073/pnas.94.4.1544.
9
Sites of antinociceptive action of systemically injected morphine: involvement of supraspinal loci as revealed by intracerebroventricular injection of naloxone.
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10
Alpha 2-adrenoceptor modulation of nociception in rat spinal cord: location, effects and interactions with morphine.大鼠脊髓中α2肾上腺素能受体对伤害感受的调节：定位、作用及与吗啡的相互作用
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一种μ阿片肽[Dmt(1)]DALDA与吗啡的不同镇痛作用。

Differential analgesic effects of a mu-opioid peptide, [Dmt(1)]DALDA, and morphine.

作者信息

Shimoyama Megumi, Szeto Hazel H, Schiller Peter W, Tagaito Yugo, Tokairin Hideyuki, Eun Chong moon, Shimoyama Naohito

机构信息

Department of Anesthesiology, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan.

出版信息

Pharmacology. 2009;83(1):33-7. doi: 10.1159/000167878. Epub 2008 Nov 6.

DOI:10.1159/000167878
PMID:18987489
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2834256/
Abstract

AIMS

H-Dmt-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA), a highly selective micro-opioid peptide, is potently analgesic after systemic and intrathecal administration but is less potent given intracerebroventricularly. This study was performed to further characterize the analgesic effects of [Dmt(1)]DALDA.

METHODS

We compared the effects of [Dmt(1)]DALDA and morphine after systemic administration in two different acute pain tests, the tail flick test and the paw withdrawal test, and examined how antagonizing the spinal opioid actions would affect their analgesic effects.

RESULTS

[Dmt(1)]DALDA was markedly more potent in the tail flick test than in the hot plate test, while the potencies of morphine were similar in the two tests. Intrathecal naloxone completely blocked the effect of systemic [Dmt(1)]DALDA in the tail flick test, while it only partially blocked the effect of morphine. At higher doses that produced analgesia in the hot plate test, the effect of [Dmt(1)]DALDA in this test was only partially blocked by naloxone.

CONCLUSION

Systemic [Dmt(1)]DALDA has a unique analgesic property clearly different from that of morphine and it has a propensity to produce spinal analgesia.

摘要

目的

H-Dmt-D-Arg-Phe-Lys-NH(2)（[Dmt(1)]DALDA），一种高度选择性的微阿片肽，经全身和鞘内给药后具有强效镇痛作用，但经脑室内给药时效力较弱。本研究旨在进一步表征[Dmt(1)]DALDA的镇痛作用。

方法

我们在两种不同的急性疼痛试验，即甩尾试验和爪部撤离试验中比较了[Dmt(1)]DALDA和吗啡经全身给药后的效果，并研究拮抗脊髓阿片类作用如何影响它们的镇痛效果。

结果

[Dmt(1)]DALDA在甩尾试验中的效力明显高于热板试验，而吗啡在这两种试验中的效力相似。鞘内注射纳洛酮完全阻断了全身给药的[Dmt(1)]DALDA在甩尾试验中的作用，而仅部分阻断了吗啡的作用。在热板试验中产生镇痛作用的较高剂量下，纳洛酮仅部分阻断了[Dmt(1)]DALDA在该试验中的作用。

结论

全身给药的[Dmt(1)]DALDA具有与吗啡明显不同的独特镇痛特性，且有产生脊髓镇痛的倾向。