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]
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
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.