Spinal co-administration of peptide substance P antagonist increases antinociceptive effect of the opioid peptide biphalin

Misterek, K; Maszczynska, Iwona; Dorociak, A; Gumulka, S. W.; Carr, Daniel B.; Szyfelbein, S.K.; Lipkowski, Andrzej W.

doi:10.1016/0024-3205(94)00494-3

Cited by 42 publications

(34 citation statements)

References 21 publications

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“…This finding is however in agreement with prior work. 43 When testing a combination of opioid peptides with a tachykinin antagonist we have shown that a low dose (not antinociceptive when applied individually) of tachykinin antagonist strongly potentiated opioid antinociception. Increasing the dose of the SP antagonist resulted in neurotoxic side effects rather than potentiation of antinociception.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist – Neurokinin-1 antagonist peptidomimetics

Guillemyn

Kleczkowska

Leśniak

et al. 2015

European Journal of Medicinal Chemistry

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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 behavioral 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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Section: Discussionmentioning

confidence: 99%

Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist – Neurokinin-1 antagonist peptidomimetics

Guillemyn

Kleczkowska

Leśniak

et al. 2015

European Journal of Medicinal Chemistry

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“…Therefore, simultaneous partial blocking of presynaptic substance P release and blocking of postsynaptic substance P receptors responsible for signal transmission has been the first multitarget approach. Indeed, co-injection of a weak peptide substance P antagonist together with an opioid peptide strongly enhances opioid analgesia [15]. Consequently, the development of multitarget ligands results in the development of a new type of effective analgesics [6].…”

Section: Introductionmentioning

confidence: 99%

Original article Opioid agonist – tachykinin antagonist as a new analgesic with adjuvant anticancer properties

Matalińska

Skurzak²,

Markowicz³

et al. 2013

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“…Coadministration of a δ / μ opioid agonist and a neurokinin 1 (NK1) antagonist has been reported to produce the facilitatory role of the substance P-NK1 system in opioid signal transmission [60,61]. This combination explains many important biological effects such as high potency in acute pain models and inhibition of opioid-induced tolerance in chronic tests using rats.…”

Section: Emerging Drug Design Strategies: Alliance Of Opioid Agonimentioning

confidence: 99%

Investigational peptide and peptidomimetic μ and δ opioid receptor agonists in the relief of pain

Giri¹,

Hruby²

2013

Expert Opinion on Investigational Drugs

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Introduction Current methods for treating prolonged and neuropathic pain are inadequate and lead to toxicities that greatly diminish quality of life. Therefore, new approaches to the treatment of pain states are needed to address these problems. Areas covered The review primarily reviews approaches that have been taken in the peer-reviewed literature of multivalent ligands that interact with both μ and δ opioid receptors as agonists, and in some cases, also with pharmacophores for antagonist ligands that interact with other receptors as antagonists to block pain. Expert opinion Although there are a number of drugs currently on the market for the treatment of pain; none of them are 100% successful. In the authors’ opinion, it is clear that new directions and modalities are needed to better address the treatment of prolonged and neuropathic pain; one drug or class clearly is not the answer for all pain therapy. Undoubtedly, there are many different phenotypes of prolonged and neuropathic pain and this should be one avenue to further develop appropriate therapies.

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Spinal co-administration of peptide substance P antagonist increases antinociceptive effect of the opioid peptide biphalin

Cited by 42 publications

References 21 publications

Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist – Neurokinin-1 antagonist peptidomimetics

Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist – Neurokinin-1 antagonist peptidomimetics

Original article Opioid agonist – tachykinin antagonist as a new analgesic with adjuvant anticancer properties

Investigational peptide and peptidomimetic μ and δ opioid receptor agonists in the relief of pain

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