5'-Guanidinonaltrindole

5'-Guanidinonaltrindole (5'-GNTI) is an opioid antagonist used in scientific research which is highly selective for the κ opioid receptor. It is 5x more potent and 500 times more selective than the commonly used κ-opioid antagonist norbinaltorphimine.[1] It has a slow onset and long duration of action,[2][3] and produces antidepressant effects in animal studies.[4] It also increases allodynia by interfering with the action of the κ-opioid peptide dynorphin.[5]

5'-Guanidinonaltrindole
Clinical data
Other names5'-Guanidinonaltrindole, GNTI
Identifiers
IUPAC name
  • 5'-Guanidinyl-17-(cyclopropylmethyl)-6,7-dehydro-4,5α-epoxy-3,14-dihydroxy-6,7-2',3'-indolomorphinan
PubChem CID
IUPHAR/BPS
ChemSpider
ChEMBL
Chemical and physical data
FormulaC27H29N5O3
Molar mass471.561 g·mol−1
3D model (JSmol)
SMILES
  • c1cc2c(cc1NC(=N)N)c3c([nH]2)[C@H]4[C@@]56CCN([C@@H]([C@@]5(C3)O)Cc7c6c(c(cc7)O)O4)CC8CC8
InChI
  • InChI=1S/C27H29N5O3/c28-25(29)30-15-4-5-18-16(10-15)17-11-27(34)20-9-14-3-6-19(33)23-21(14)26(27,24(35-23)22(17)31-18)7-8-32(20)12-13-1-2-13/h3-6,10,13,20,24,31,33-34H,1-2,7-9,11-12H2,(H4,28,29,30)/t20-,24+,26+,27-/m1/s1 N
  • Key:VLNHDKDBGWXJEE-GYHUNEDQSA-N N
 NY (what is this?)  (verify)

In addition to activity at the KOR, 5'-GNTI has been found to act as a positive allosteric modulator of the α1A-adrenergic receptor (EC50 = 41 nM), and this may contribute to its "severe transient effects".[6]

See also

References
  1. Jones RM, Portoghese PS (May 2000). "5'-Guanidinonaltrindole, a highly selective and potent kappa-opioid receptor antagonist". European Journal of Pharmacology. 396 (1): 49–52. doi:10.1016/S0014-2999(00)00208-9. PMID 10822054.
  2. Negus SS, Mello NK, Linsenmayer DC, Jones RM, Portoghese PS (October 2002). "Kappa opioid antagonist effects of the novel kappa antagonist 5'-guanidinonaltrindole (GNTI) in an assay of schedule-controlled behavior in rhesus monkeys". Psychopharmacology. 163 (3–4): 412–9. doi:10.1007/s00213-002-1038-x. PMID 12373442. S2CID 6342513.
  3. Bruchas MR, Yang T, Schreiber S, Defino M, Kwan SC, Li S, Chavkin C (October 2007). "Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase". The Journal of Biological Chemistry. 282 (41): 29803–11. doi:10.1074/jbc.M705540200. PMC 2096775. PMID 17702750.
  4. Mague SD, Pliakas AM, Todtenkopf MS, Tomasiewicz HC, Zhang Y, Stevens WC, et al. (April 2003). "Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats". The Journal of Pharmacology and Experimental Therapeutics. 305 (1): 323–30. doi:10.1124/jpet.102.046433. PMID 12649385. S2CID 7235990.
  5. Obara I, Mika J, Schafer MK, Przewlocka B (October 2003). "Antagonists of the kappa-opioid receptor enhance allodynia in rats and mice after sciatic nerve ligation". British Journal of Pharmacology. 140 (3): 538–46. doi:10.1038/sj.bjp.0705427. PMC 1574046. PMID 12970097.
  6. Munro TA, Huang XP, Inglese C, Perrone MG, Van't Veer A, Carroll FI, et al. (2013). "Selective κ opioid antagonists nor-BNI, GNTI and JDTic have low affinities for non-opioid receptors and transporters". PLOS ONE. 8 (8): e70701. Bibcode:2013PLoSO...870701M. doi:10.1371/journal.pone.0070701. PMC 3747596. PMID 23976952.


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