IBNtxA

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]

IBNtxA

Clinical data
ATC code	none
Identifiers
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
PubChem CID	51003467
ChemSpider	26617995
Chemical and physical data
Formula	C27H29IN2O4
Molar mass	572.443 g·mol^−1
3D model (JSmol)	Interactive image
SMILES 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 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

References

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. 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