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{{Short description|Chemical compound}}
{{Drugbox
{{Drugbox
| IUPAC_name = 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
| IUPAC_name = 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
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| PubChem = 51003467
| PubChem = 51003467
| ChemSpiderID = 26617995
| ChemSpiderID = 26617995
| ChEMBL = 1795711


<!--Chemical data-->
<!--Chemical data-->
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'''IBNtxA''', or '''3-iodobenzoyl naltrexamine''', is an atypical [[opioid]] [[analgesic]] drug derived from [[naltrexone]]. In animal studies it produces potent analgesic effects that are blocked by [[levallorphan]]<ref name="pmid22734622">{{cite journal |vauthors=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 |title=Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated μ opioid receptor (MOR-1) splice variants |journal=J. Med. Chem. |volume=55 |issue=14 |pages=6352–62 |year=2012 |pmid=22734622 |pmc=3412067 |doi=10.1021/jm300305c }}</ref> and so appear to be [[mu opioid receptor|μ-opioid]] mediated, but it fails to produce [[constipation]] or [[respiratory depression]], and is neither rewarding or aversive<ref>{{cite journal | pmid = 22106286 | doi=10.1073/pnas.1115231108 | volume=108 | issue=49 | title=Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects | pmc=3241767 | date=December 2011 | journal=Proc. Natl. Acad. Sci. U.S.A. | pages=19778–83 | vauthors=Majumdar S, Grinnell S, Le Rouzic V | bibcode=2011PNAS..10819778M | display-authors = etal | doi-access=free }}</ref> in [[conditioned place preference]] protocols.<ref name="pmid24970924">{{cite journal |vauthors=Grinnell SG, Majumdar S, Narayan A, Le Rouzic V, Ansonoff M, Pintar JE, Pasternak GW |title=Pharmacologic characterization in the rat of a potent analgesic lacking respiratory depression, IBNtxA |journal=J. Pharmacol. Exp. Ther. |volume=350 |issue=3 |pages=710–8 |year=2014 |pmid=24970924 |doi=10.1124/jpet.114.213199 |pmc=4152881}}</ref> These unusual properties are thought to result from agonist action at a [[splice variant]] or [[heterodimer]] of the μ-opioid receptor,<ref name="pmid25093831">{{cite journal |vauthors=Wieskopf JS, Pan YX, Marcovitz J, Tuttle AH, Majumdar S, Pidakala J, Pasternak GW, Mogil JS |title=Broad-spectrum analgesic efficacy of IBNtxA is mediated by exon 11-associated splice variants of the mu-opioid receptor gene |journal=Pain |volume=155 |issue=10 |pages=2063–70 |year=2014 |pmid=25093831 |doi=10.1016/j.pain.2014.07.014 |pmc=4372857}}</ref> rather than at the classical full length form targeted by conventional opioid drugs.<ref>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</ref>
'''IBNtxA''', or '''3-iodobenzoyl naltrexamine''', is an atypical [[opioid]] [[analgesic]] drug derived from [[naltrexone]]. In animal studies it produces potent analgesic effects that are blocked by [[levallorphan]]<ref name="pmid22734622">{{cite journal |vauthors=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 |title=Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated μ opioid receptor (MOR-1) splice variants |journal=J. Med. Chem. |volume=55 |issue=14 |pages=6352–62 |year=2012 |pmid=22734622 |pmc=3412067 |doi=10.1021/jm300305c }}</ref> and so appear to be [[mu opioid receptor|μ-opioid]] mediated, but it fails to produce [[constipation]] or [[respiratory depression]], and is neither rewarding or aversive<ref>{{cite journal | pmid = 22106286 | doi=10.1073/pnas.1115231108 | volume=108 | issue=49 | title=Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects | pmc=3241767 | date=December 2011 | journal=Proc. Natl. Acad. Sci. U.S.A. | pages=19778–83 | vauthors=Majumdar S, Grinnell S, Le Rouzic V | bibcode=2011PNAS..10819778M | display-authors = etal | doi-access=free }}</ref> in [[conditioned place preference]] protocols.<ref name="pmid24970924">{{cite journal |vauthors=Grinnell SG, Majumdar S, Narayan A, Le Rouzic V, Ansonoff M, Pintar JE, Pasternak GW |title=Pharmacologic characterization in the rat of a potent analgesic lacking respiratory depression, IBNtxA |journal=J. Pharmacol. Exp. Ther. |volume=350 |issue=3 |pages=710–8 |year=2014 |pmid=24970924 |doi=10.1124/jpet.114.213199 |pmc=4152881}}</ref> These unusual properties are thought to result from agonist action at a [[splice variant]] or [[heterodimer]] of the μ-opioid receptor,<ref name="pmid25093831">{{cite journal |vauthors=Wieskopf JS, Pan YX, Marcovitz J, Tuttle AH, Majumdar S, Pidakala J, Pasternak GW, Mogil JS |title=Broad-spectrum analgesic efficacy of IBNtxA is mediated by exon 11-associated splice variants of the mu-opioid receptor gene |journal=Pain |volume=155 |issue=10 |pages=2063–70 |year=2014 |pmid=25093831 |doi=10.1016/j.pain.2014.07.014 |pmc=4372857}}</ref> rather than at the classical full length form targeted by conventional opioid drugs.<ref>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</ref>


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. Azido Aryl Analogues of IBNtxA retain significant activity at the MOR.<ref>{{cite journal |vauthors=Grinnell S.G.,Uprety Rajendra|title=Synthesis and Characterization of Azido Aryl Analogs of IBNtxA for Radio-Photoaffinity Labeling Opioid Receptors in Cell Lines and in Mouse Brain |journal=Cell Mol Neurobiology |volume=5 |issue=41 |pages=977-993 |year=2021 |pmid=32424771 |pmc=7671950 |doi=10.1007/s10571-020-00867-6}}</ref>
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 than [[morphine]]. Azido Aryl Analogues of IBNtxA retain significant activity at the MOR.<ref>{{cite journal |vauthors=Grinnell SG, Rajendra U|title=Synthesis and Characterization of Azido Aryl Analogs of IBNtxA for Radio-Photoaffinity Labeling Opioid Receptors in Cell Lines and in Mouse Brain |journal=Cell Mol Neurobiology |volume=5 |issue=41 |pages=977–993 |year=2021 |pmid=32424771 |pmc=7671950 |doi=10.1007/s10571-020-00867-6}}</ref>


==References==
==References==
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[[Category:Benzamides]]
[[Category:Benzamides]]
[[Category:Mu-opioid agonists]]
[[Category:Mu-opioid receptor agonists]]
[[Category:Phenols]]
[[Category:Hydroxyarenes]]
[[Category:Semisynthetic opioids]]
[[Category:Semisynthetic opioids]]
[[Category:Heterocyclic compounds with 5 rings]]
[[Category:Cyclopropyl compounds]]




Latest revision as of 16:15, 21 October 2024

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
PubChem CID
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, or 3-iodobenzoyl naltrexamine, is an atypical opioid analgesic drug derived from naltrexone. In animal studies it produces potent analgesic effects that are blocked by levallorphan[1] and so appear to be μ-opioid mediated, but it fails to produce constipation or respiratory depression, and is neither rewarding or aversive[2] in conditioned place preference protocols.[3] These unusual properties are thought to result from agonist action at a splice variant or heterodimer 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 than morphine. 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.


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