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International Journal of Medicinal Chemistry
Volume 2012, Article ID 327257, 6 pages
http://dx.doi.org/10.1155/2012/327257
Research Article

MDAN-21: A Bivalent Opioid Ligand Containing mu-Agonist and Delta-Antagonist Pharmacophores and Its Effects in Rhesus Monkeys

1Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA
2Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA

Received 4 January 2012; Accepted 14 February 2012

Academic Editor: Yoshio Okada

Copyright © 2012 Mario D. Aceto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. D. Corbett, G. Henderson, A. T. McKnight, and S. J. Paterson, “75 Years of opioid research: the exciting but vain quest for the Holy Grail,” British Journal of Pharmacology, vol. 147, supplement 1, pp. S153–S162, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. J. L. Vaught and A. E. Takemori, “A further characterization of the differential effects of leucine enkephalin, methionine enkephalin and their analogs on morphine-induced analgesia,” Journal of Pharmacology and Experimental Therapeutics, vol. 211, no. 2, pp. 280–283, 1979. View at Google Scholar · View at Scopus
  3. E. E. Abdelhamid, M. Sultana, P. S. Portoghese, and A. E. Takemori, “Selective blockage of delta opioid receptors prevents the development of morphine tolerance and dependence in mice,” Journal of Pharmacology and Experimental Therapeutics, vol. 258, no. 1, pp. 299–303, 1991. View at Google Scholar · View at Scopus
  4. D. Wang, X. Sun, L. M. Bohn, and W. Sadee, “Opioid receptor homo- and heterodimerization in living cells by quantitative bioluminescence resonance energy transfer,” Molecular Pharmacology, vol. 67, no. 6, pp. 2173–2184, 2005. View at Publisher · View at Google Scholar · View at Scopus
  5. I. Gomes, A. Gupta, J. Filipovska, H. H. Szeto, J. E. Pintar, and L. A. Devi, “A role for heterodimerization of μ and δ opiate receptors in enhancing morphine analgesia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 14, pp. 5135–5139, 2004. View at Publisher · View at Google Scholar · View at Scopus
  6. I. Gomes, B. A. Jordan, A. Gupta, N. Trapaidze, V. Nagy, and L. A. Devi, “Heterodimerization of mu and delta opioid receptors: a role in opiate synergy,” The Journal of Neuroscience, vol. 20, no. 22, Article ID RC 110, 2000. View at Google Scholar · View at Scopus
  7. B. A. Jordan and L. A. Devi, “G-protein-coupled receptor heterodimerization modulates receptor function,” Nature, vol. 399, no. 6737, pp. 697–700, 1999. View at Publisher · View at Google Scholar · View at Scopus
  8. P. S. Portoghese, “From models to molecules: opioid receptor dimers, bivalent ligands, and selective opioid receptor probes,” Journal of Medicinal Chemistry, vol. 44, no. 14, pp. 2259–2269, 2001. View at Publisher · View at Google Scholar · View at Scopus
  9. D. J. Daniels, N. R. Lenard, C. L. Etienne, P. Y. Law, S. C. Roerig, and P. S. Portoghese, “Opioid-induced tolerance and dependence in mice is modulated by the distance between pharmacophores in a bivalent ligand series,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 52, pp. 19208–19213, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. N. R. Lenard, D. J. Daniels, P. S. Portoghese, and S. C. Roerig, “Absence of conditioned place preference or reinstatement with bivalent ligands containing mu-opioid receptor agonist and delta-opioid receptor antagonist pharmacophores,” European Journal of Pharmacology, vol. 566, no. 1–3, pp. 75–82, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. M. D. Aceto, “Assessment of physical dependence techniques for the evaluation of abused drugs,” in Modern Methods in Pharmacology, M. W. Adler and A. Cowan, Eds., vol. 6 of Testing and Evaluation of Drugs of Abuse, pp. 67–79, Wiley-Lis, New York, NY, USA, 1990. View at Google Scholar
  12. G. A. Deneau, An analysis of factors influencing the development of physical dependence of narcotic analgesics in rhesus monkeys with methods of predicting physical dependence liability in man, thesis, University of Michigan, Ann Arbor, Mich, USA, 1956.
  13. M. D. Aceto, R. E. Flora, and L. S. Harris, “The effects of naloxone and nalorphine during the development of morphine dependence in rhesus monkeys,” Pharmacology, vol. 15, no. 1, pp. 1–9, 1977. View at Google Scholar · View at Scopus
  14. M. D. Aceto, L. S. Harris, and E. L. May, “Dependence studies of new compounds in the rhesus monkey, rat, and mouse,” National Institute on Drug Abuse Research Monograph Series, vol. 67, pp. 399–452, 1986. View at Google Scholar
  15. G. P. Do Carmo, R. Polt, E. J. Bilsky, K. C. Rice, and S. S. Negus, “Behavioral pharmacology of the μ/δ opioid glycopeptide MMP2200 in rhesus monkeys,” Journal of Pharmacology and Experimental Therapeutics, vol. 326, no. 3, pp. 939–948, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. E. R. Butelman, J. W. Ball, T. J. Harris, and M. J. Kreek, “Topical capsaicin-induced allodynia in unanesthetized primates: pharmacological modulation,” Journal of Pharmacology and Experimental Therapeutics, vol. 306, no. 3, pp. 1106–1114, 2003. View at Publisher · View at Google Scholar · View at Scopus
  17. P. Compton, P. Athanasos, and D. Elashoff, “Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted humans: a preliminary study,” Journal of Pain, vol. 4, no. 9, pp. 511–519, 2003. View at Publisher · View at Google Scholar · View at Scopus
  18. M. Doverty, J. M. White, A. A. Somogyi, F. Bochner, R. Ali, and W. Ling, “Hyperalgesic responses in methadone maintenance patients,” Pain, vol. 90, no. 1-2, pp. 91–96, 2001. View at Publisher · View at Google Scholar · View at Scopus
  19. J. J. Lipman and B. Blumenkopf, “Comparison of subjective and objective analgesic effects of intravenous and intrathecal morphine in chronic pain patients by heat beam dolorimetry,” Pain, vol. 39, no. 3, pp. 249–256, 1989. View at Publisher · View at Google Scholar · View at Scopus
  20. A .E. Jacobson, “Biological evaluation of compounds for their physical dependence potential and abuse liability.V11. Drug testing program of the committee on drug dependence, Inc, (1983),” National Institute on Drug Abuse Research Monograph Series, vol. 49, pp. 352–360, 1984. View at Google Scholar
  21. A. Mansour, H. Khachaturian, M. E. Lewis, H. Akil, and S. J. Watson, “Autoradiographic differentiation of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain,” Journal of Neuroscience, vol. 7, no. 8, pp. 2445–2464, 1987. View at Google Scholar · View at Scopus
  22. J. B. Daunais, S. R. Letchworth, L. J. Sim-Selley, H. R. Smith, S. R. Childers, and L. J. Porrino, “Functional and anatomical localization of mu opioid receptors in the striatum, amygdala, and extended amygdala of the nonhuman primate,” Journal of Comparative Neurology, vol. 433, no. 4, pp. 471–485, 2001. View at Publisher · View at Google Scholar · View at Scopus
  23. D. Peckys and G. B. Landwehrmeyer, “Expression of mu, kappa, and delta opioid receptor messenger RNA in the human CNS: a 33P in situ hybridization study,” Neuroscience, vol. 88, no. 4, pp. 1093–1135, 1999. View at Publisher · View at Google Scholar · View at Scopus