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Citation
Tags
HERO ID
7046378
Reference Type
Journal Article
Title
Targeting multiple opioid receptors - improved analgesics with reduced side effects?
Author(s)
Guenther, T; Dasgupta, P; Mann, A; Miess, E; Kliewer, A; Fritzwanker, S; Steinborn, R; Schulz, S; ,
Year
2018
Is Peer Reviewed?
Yes
Journal
British Journal of Pharmacology
ISSN:
0007-1188
EISSN:
1476-5381
Publisher
WILEY
Location
HOBOKEN
Page Numbers
2857-2868
PMID
28378462
DOI
10.1111/bph.13809
Web of Science Id
WOS:000436105700013
Abstract
Classical opioid analgesics, including morphine, mediate all of their desired and undesired effects by specific activation of the -opioid receptor ( receptor). The use of morphine for treating chronic pain, however, is limited by the development of constipation, respiratory depression, tolerance and dependence. Analgesic effects can also be mediated through other members of the opioid receptor family such as the -opioid receptor ( receptor), -opioid receptor ( receptor) and the nociceptin/orphanin FQ peptide receptor (NOP receptor). Currently, a new generation of opioid analgesics is being developed that can simultaneously bind with high affinity to multiple opioid receptors. With this new action profile, it is hoped that additional analgesic effects and fewer side effects can be achieved. Recent research is mainly focused on the development of bifunctional /NOP receptor agonists, which has already led to novel lead structures such as the spiroindole-based cebranopadol and a compound class with a piperidin-4-yl-1,3-dihydroindol-2-one backbone (SR16835/AT-202 and SR14150/AT-200). In addition, the ornivol BU08028 is an analogue of the clinically well-established buprenorphine. Moreover, the morphinan-based nalfurafine exerts its effect with a dominant receptor-component and is therefore utilized in the treatment of pruritus. The very potent dihydroetorphine is a true multi-receptor opioid ligand in that it binds to , and receptors. The main focus of this review is to assess the paradigm of opioid ligands targeting multiple receptors with a single chemical entity. We reflect on this rationale by discussing the biological actions of particular multi-opioid receptor ligands, but not on their medicinal chemistry and design.
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