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IBNtxA

From Wikipedia, the free encyclopedia
Chemical compound
Pharmaceutical compound
IBNtxA
Clinical data
ATC code
  • none
Identifiers
  • N-[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-yl]-3-iodobenzamide
CAS Number
PubChemCID
ChemSpider
ChEMBL
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC27H29IN2O4
Molar mass572.443 g·mol−1
3D model (JSmol)
  • C1C[C@]2([C@H]3CC4=C5[C@@]2(CCN3CC6CC6)[C@H]([C@@H]1NC(=O)C7=CC(=CC=C7)I)OC5=C(C=C4)O)O
  • InChI=1S/C27H29IN2O4/c28-18-3-1-2-17(12-18)25(32)29-19-8-9-27(33)21-13-16-6-7-20(31)23-22(16)26(27,24(19)34-23)10-11-30(21)14-15-4-5-15/h1-3,6-7,12,15,19,21,24,31,33H,4-5,8-11,13-14H2,(H,29,32)/t19-,21-,24+,26+,27-/m1/s1
  • Key:FGAFDGWRFOJPRY-XGTKUTNFSA-N

IBNtxA, or3-iodobenzoyl naltrexamine, is an atypicalopioidanalgesic drug derived fromnaltrexone. In animal studies it produces potent analgesic effects that are blocked bylevallorphan[1] and so appear to beμ-opioid mediated, but it fails to produceconstipation orrespiratory depression, and is neither rewarding or aversive[2] inconditioned place preference protocols.[3] These unusual properties are thought to result from agonist action at asplice variant orheterodimer of the μ-opioid receptor,[4] rather than at the classical full length form targeted by conventional opioid drugs.[5]

In the Radioligand binding assay it has shown to have affinities of 0.11nM at the MOR, 0.24nM at the DOR and 0.03nM at the KOR and in the Hot- Plate Assay it is shown to be around 20x more potent thanmorphine. Azido Aryl Analogues of IBNtxA retain significant activity at the MOR.[6]

References

[edit]
  1. ^Majumdar S, Subrath J, Le Rouzic V, Polikar L, Burgman M, Nagakura K, Ocampo J, Haselton N, Pasternak AR, Grinnell S, Pan YX, Pasternak GW (2012)."Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated μ opioid receptor (MOR-1) splice variants".J. Med. Chem.55 (14):6352–62.doi:10.1021/jm300305c.PMC 3412067.PMID 22734622.
  2. ^Majumdar S, Grinnell S, Le Rouzic V, et al. (December 2011)."Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects".Proc. Natl. Acad. Sci. U.S.A.108 (49):19778–83.Bibcode:2011PNAS..10819778M.doi:10.1073/pnas.1115231108.PMC 3241767.PMID 22106286.
  3. ^Grinnell SG, Majumdar S, Narayan A, Le Rouzic V, Ansonoff M, Pintar JE, Pasternak GW (2014)."Pharmacologic characterization in the rat of a potent analgesic lacking respiratory depression, IBNtxA".J. Pharmacol. Exp. Ther.350 (3):710–8.doi:10.1124/jpet.114.213199.PMC 4152881.PMID 24970924.
  4. ^Wieskopf JS, Pan YX, Marcovitz J, Tuttle AH, Majumdar S, Pidakala J, Pasternak GW, Mogil JS (2014)."Broad-spectrum analgesic efficacy of IBNtxA is mediated by exon 11-associated splice variants of the mu-opioid receptor gene".Pain.155 (10):2063–70.doi:10.1016/j.pain.2014.07.014.PMC 4372857.PMID 25093831.
  5. ^Keck TM, Uddin MM, Babenko E, Wu C, Moura-Letts G. Abuse Liability and Anti-Addiction Potential of the Atypical Mu Opioid Receptor Agonist IBNtxA.The FASEB Journal 31 (1 Supplement), 985.4-985.4, 2017
  6. ^Grinnell SG, Rajendra U (2021)."Synthesis and Characterization of Azido Aryl Analogs of IBNtxA for Radio-Photoaffinity Labeling Opioid Receptors in Cell Lines and in Mouse Brain".Cell Mol Neurobiology.5 (41):977–993.doi:10.1007/s10571-020-00867-6.PMC 7671950.PMID 32424771.
μ-opioid
(MOR)
Agonists
(abridged;
full list)
Antagonists
δ-opioid
(DOR)
Agonists
Antagonists
κ-opioid
(KOR)
Agonists
Antagonists
Nociceptin
(NOP)
Agonists
Antagonists
Others


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