Volume 11 Supplement 2

17th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access

Efficacy of systemic HS-198, an analogue of oxymorphone, on cancer pain-related behaviour in mice

  • Muhammad F Asim1,
  • Catalina R Bohotin1,
  • Cristina E Constantin2,
  • Helmut Schmidhammer1,
  • Michaela Kress2 and
  • Mariana Spetea1Email author
BMC Pharmacology201111(Suppl 2):A4

https://doi.org/10.1186/1471-2210-11-S2-A4

Published: 5 September 2011

Background

Cancer pain is a significant clinical problem being one of the first symptoms of disease with 75–90% of the patients experiencing chronic pain syndromes in advanced stages [1]. The management of cancer pain is mainly based on the use of opioid drugs; however their clinical use is limited by high incidence of adverse effects. There is a continued search for highly efficacious opioid analgesics with reduced complications and improved patient compliance. An analogue of the clinically used oxymorphone, 5-methyl-substituted 14-O-methyloxymorphone (HS-198), is a selective μ opioid agonist and a potent antinociceptive agent in animal models of nociceptive and inflammatory pain, while exhibiting a favourable dissociation between analgesia and the occurrence of side effects [2]. We report data on efficacy of this opioid agonist after subcutaneous administration (s.c.) in a murine model of cancer pain. The opioid receptor-mechanistic basis of the antinociceptive action was also investigated.

Methods

Cancer pain was induced in C57BL/6J mice by s.c. implantation of lung carcinoma cells, in the plantar and dorsal side of the right hindpaw [3]. Mechanical sensitivity was determined using von Frey monofilaments. Heat sensitivity was assessed using the Hargreaves test. In vitro biological activities were evaluated using binding and functional assays.

Results

On day 9 post-inoculation, s.c. HS-198 produced a dose-dependent inhibition with significant effects in attenuating cancer pain-related behaviour (thermal and mechanical hypersensitivity) on the tumour side. Pre-treatment with the opioid receptor antagonist naloxone reversed the antinociceptive effects induced by HS-198 in mice with cancer-induced pain. In vitro, HS-198 showed high affinity and selectivity for both mouse and rat μ opioid receptors, and it displayed potent μ-agonism through inhibition of G proteins.

Conclusions

Systemic s.c. administration of the μ opioid receptor agonist HS-198 induces potent antinociceptive effects in mice with cancer pain via opioid receptor-specific mechanisms.

Declarations

Acknowledgements

Supported by the Austrian Science Fund (FWF: TRP 19-B18).

Authors’ Affiliations

(1)
Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences, University of Innsbruck
(2)
Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University

References

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  2. Schmidhammer H, Spetea M: Synthesis of 14-alkoxymorphinan derivatives and their pharmacological actions. Top Curr Chem. 2011, 299: 63-91.View ArticlePubMedGoogle Scholar
  3. Constantin CE, Mair N, Sailer CA, Andratsch M, Xu ZZ, Blumer MJ, Scherbakov N, Davis JB, Bluethmann H, Ji RR, Kress M: Endogenous tumor necrosis factor α (TNFα) requires TNF receptor type 2 to generate heat hyperalgesia in a mouse cancer model. J Neurosci. 2008, 28: 5072-5081. 10.1523/JNEUROSCI.4476-07.2008.View ArticlePubMedGoogle Scholar

Copyright

© Asim et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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