ArticleEuropean journal of medicinal chemistry2015
Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist - neurokinin-1 antagonist peptidomimetics.
Article in European journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 30 citations in OpenAlex.
- Harnessing the Anti-Nociceptive Potential of NK2 and NK3 Ligands in the Design of New Multifunctional μ/δ-Opioid Agonist-Neurokinin Antagonist Peptidomimetics.Molecules (Basel, Switzerland) · 2021Article
- Optimized Opioid-Neurotensin Multitarget Peptides: From Design to Structure-Activity Relationship Studies.Journal of medicinal chemistry · 2020Article
- In Vivo, In Vitro and In Silico Studies of the Hybrid Compound AA3266, an Opioid Agonist/NK1R Antagonist with Selective Cytotoxicity.International journal of molecular sciences · 2020Article
- Antinociceptive and Cytotoxic Activity of Opioid Peptides with Hydrazone and Hydrazide Moieties at the C-Terminus.Molecules (Basel, Switzerland) · 2020Article
- Mechanistic Understanding of Peptide Analogues, DALDA, [DmtMolecules (Basel, Switzerland) · 2020Article
- Synthesis and Pharmacological Evaluation of Hybrids Targeting Opioid and Neurokinin Receptors.Molecules (Basel, Switzerland) · 2019Article
- Elucidating the active δ-opioid receptor crystal structure with peptide and small-molecule agonists.Science advances · 2019Article
- Analgesic Properties of Opioid/NK1 Multitarget Ligands with Distinct in Vitro Profiles in Naive and Chronic Constriction Injury Mice.ACS chemical neuroscience · 2017Article
- Bifunctional Peptide-Based Opioid Agonist-Nociceptin Antagonist Ligands for Dual Treatment of Acute and Neuropathic Pain.Journal of medicinal chemistry · 2016Article
- Dual Alleviation of Acute and Neuropathic Pain by Fused Opioid Agonist-Neurokinin 1 Antagonist Peptidomimetics.ACS medicinal chemistry letters · 2015Article
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 4 countries.
Funding
Abstract
A reported mixed opioid agonist - neurokinin 1 receptor (NK1R) antagonist 4 (Dmt-D-Arg-Aba-Gly-(3',5'-(CF3)2)NMe-benzyl) was modified to identify important features in both pharmacophores. The new dual ligands were tested in vitro and subsequently two compounds (lead structure 4 and one of the new analogues 22, Dmt-D-Arg-Aba-β-Ala-NMe-Bn) were selected for in vivo behavioural assays, which were conducted in acute (tail-flick) and neuropathic pain models (cold plate and von Frey) in rats. Compared to the parent opioid compound 33 (without NK1R pharmacophore), hybrid 22 was more active in the neuropathic pain models. Attenuation of neuropathic pain emerged from NK1R antagonism as demonstrated by the pure NK1R antagonist 6. Surprisingly, despite a lower in vitro activity at NK1R in comparison with 4, compound 22 was more active in the neuropathic pain models. Although potent analgesic effects were observed for 4 and 22, upon chronic administration, both manifested a tolerance profile similar to that of morphine and cross tolerance with morphine in a neuropathic pain model in rat.
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Registered trials
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