Endomorphin derivatives with improved pharmacological properties

Varamini, Pegah, Blanchfield, Joanne T. and Toth, Istvan (2013) Endomorphin derivatives with improved pharmacological properties. Current Medicinal Chemistry, 20 22: 2741-2758. doi:10.2174/0929867311320220002

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Author Varamini, Pegah
Blanchfield, Joanne T.
Toth, Istvan
Title Endomorphin derivatives with improved pharmacological properties
Journal name Current Medicinal Chemistry   Check publisher's open access policy
ISSN 0929-8673
Publication date 2013-07
Year available 2013
Sub-type Article (original research)
DOI 10.2174/0929867311320220002
Volume 20
Issue 22
Start page 2741
End page 2758
Total pages 18
Place of publication Netherlands
Publisher Bentham Science Publishers
Collection year 2014
Language eng
Formatted abstract
Centrally acting opioids, such as morphine, are the most frequently used analgesic agents for the treatment of severe pain. However, their usefulness is limited by the production of a range of adverse effects such as constipation, respiratory depression, tolerance and physical dependence. In addition, opioids generally exhibit poor efficacy against neuropathic pain. Endomorphin-1 and -2, two endogenous opioid peptides, have been shown to produce potent antinociception in rodent models of acute and neuropathic pain with less undesirable side effects than opioid alkaloids. However, native endomorphins are poorly suited to clinical applications without modifications. Like all small peptides, endomorphins suffer from poor metabolic stability and a relative inability to penetrate the gastro-intestinal mucosa and blood-brain-barrier. Since the discovery of endomorphins in 1997, a huge number of endomorphin analogs have been designed and synthesized with the aim of developing compounds with improved barrier penetration and resistance to enzymatic degradation. In this review we describe various strategies that have been adopted so far to conquer the major drawbacks associated with endomorphins. They include chemical modifications to produce locally or globally-restricted peptide analogs in addition to application of peptidase inhibitors, which is of minor importance compared to the former strategy. Diverse approaches that resulted in the design and synthesis of pharmacologically active endomorphin analogs with less adverse effects are also discussed giving an insight into the development of opioid peptides with an improved side effect profile.
Keyword Endomorphin
Neuropathic pain
Peptide delivery
Mu-opioid receptor
Acute antinociceptive tolerance
Sensitive cyclic prodrugs
Analogs produce analgesia
Designed multiple ligand
Dipeptidyl peptidase-IV
Lipidic amino-acid
Pro amide bond
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 9 times in Scopus Article | Citations
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Created: Sun, 21 Jul 2013, 00:06:53 EST by System User on behalf of School of Chemistry & Molecular Biosciences