A κ opioid pharmacophore becomes a spinally selective κ-δ Agonist when modified with a basic extender arm

ACS Medicinal Chemistry Letters

Volumn 2, Issue 1, 2011, Pages 7-10

  Tang, Ye ^a   Yang, Jie ^a   Lunzer, Mary M ^a   Powers, Michael D ^a   Portoghese, Philip S ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

Author keywords

heteromers; molecular extender arm; Opioid receptors

Indexed keywords

3,4 DICHLORO N METHYL N [1 PHENYL 2 (1 PYRROLIDINYL)ETHYL]BENZENEACETAMIDE; DELTA OPIATE RECEPTOR; KAPPA OPIATE RECEPTOR; KDA 11; KDA 14; KDA 16; KDA 18; OPIATE AGONIST; UNCLASSIFIED DRUG;

ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATOM; CALCIUM TRANSPORT; CONTROLLED STUDY; DRUG POTENCY; HUMAN; HUMAN CELL; MOUSE; NOCICEPTION; NONHUMAN; PRIORITY JOURNAL; TAIL FLICK TEST;

EID: 78651480522     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml1001294     Document Type: Article

References (19)

1. Jordan, B. A.; Devi, L. A. G-protein-coupled receptor heterodimerization modulates receptor function Nature 1999, 399, 697-700
2. George, S. R.; Fan, T.; Xie, Z.; Tse, R.; Tam, V.; Varghese, G.; O'Dowd, B. F. Oligomerization of mu-and delta-opioid receptors. Generation of novel functional properties J. Biol. Chem. 2000, 275, 26128-26135
3. Gomes, I.; Jordan, B. A.; Gupta, A.; Trapaidze, N.; Nagy, V.; Devi, L. A. Heterodimerization of mu and delta opioid receptors: A role in opiate synergy J. Neurosci. 2000, 20, RC110
4. Wang, D.; Sun, X.; Bohn, L. M.; Sadee, W. Opioid receptor homo-and heterodimerization in living cells by quantitative bioluminescence resonance energy transfer Mol. Pharmacol. 2005, 67, 2173-2184
5. 1 receptor phenotypes J. Med. Chem. 2005, 48, 1713-1716
6. 2 phenotypes. Selective targeting of δ-κ heterodimers J. Med. Chem. 2004, 47, 2969-2972
7. Xie, Z.; Bhushan, R. G.; Daniels, D. J.; Portoghese, P. S. Interaction of bivalent ligand KDN21 with heterodimeric δ-κ opioid receptors in human embryonic kidney 293 cells Mol. Pharmacol. 2005, 68, 1079-1086
8. Daniels, D. J.; Lenard, N. R.; Etienne, C. L.; Law, P.-Y.; Roerig, S. C.; Portoghese, P. S. Opioid-induced tolerance and dependence in mice is modulated by the distance between pharmacophores in a bivalent ligand series Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 19208-19213
9. Zhang, S.; Yekkirala, A.; Tang, Y.; Portoghese, P. S. A bivalent ligand (KMN-21) antagonist for μ-κ heterodimeric opioid receptors Bioorg. Med. Chem. Lett. 2009, 19, 6978-6980
10. Yaguo Zheng, E. A.; Harikumar, K. G.; Hopson, J.; Powers, M. D.; Lunzer, M. M.; Miller, L. J.; Portoghese., P. S. Induced association of μ opioid (MOP) and type 2 cholecystokinin (CCK2) receptors by novel bivalent ligands J. Med. Chem. 2009, 52, 247-258
11. Waldhoer, M.; Fong, J.; Jones, R. M.; Lunzer, M. M.; Sharma, S. K.; Kostenis, E.; Portoghese, P. S.; Whistler, J. L. A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 9050-9055
12. Lunzer, M. M.; Portoghese, P. S. Selectivity of δ and κ opioid ligands depends on the route of central administration in mice J. Pharmacol. Exp. Ther. 2007, 322, 166-171
13. Wessendorf, M. W; Dooyema, J. Coexistence of kappa-and delat-opioid receptors in rat spinal cord axons Neurosci. Lett. 2001, 298, 151-154
14. Barlow, J. J.; Blackburn, R. P.; Costello, G. F.; James, R.; Le Count, D. J.; Main, B. G.; Pearce, R. J.; Russell, K.; Shaw, J. S. Structure/Activity Studies Related to 2-(3,4-dichlorophenyl)-N -methyl-N -[2-(1-pyrrolidinyl)-1- substituted-ethyl]acetamides: A Novel Series of Potent and Selective κ-Opioid Agonists J. Med. Chem. 1991, 34, 3149-3158
15. Nomenclature employed in this series is as follows: K, κ receptor; D, δ receptor; and A, agonist; the digits refer to the numbers of atoms between the pharmacophore and the terminal amino group.
16. Portoghese, P. S.; Lipkowski, A. W.; Takemori, A. E. Binaltorphimine and nor binaltorphimine, potent and selective kappaopioid receptor antagonists Life Sci. 1987, 40, 1287-1292
17. Portoghese, P. S.; Sultana, M.; Takemori, A. E. Design of peptidomimetic δ opioid receptor antagonists using the message-address concept J. Med. Chem. 1990, 33, 1714-1720
18. Gulya, K.; Krivan, M.; Nyolczas, N.; Sarnyai, Z.; Kovacs, G. L. Central effects of the potent and highly selective mu opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) in mice Eur. J. Pharmacol. 1988, 150, 355-360
19. Yekkirala, A. S.; Kalyuzhny, A. E.; Portoghese, P. S. Standard Opioid Agonists Activate Heteromeric Opioid Receptors: Evidence for Morphine and [D-Ala2-MePhe4-Glyol5]Enkephalin as Selective μ-δ Agonists ACS Chem. Neurosci. 2010, 1 (2) 146-154