5'-Guanidinonaltrindole

5'-Guanidinonaltrindole
Clinical data
Other names	5'-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	6604846;
IUPHAR/BPS	1669;
ChemSpider	21259050 ;
ChEMBL	ChEMBL330427 ;
CompTox Dashboard (EPA)	DTXSID101018243 ;
Chemical and physical data
Formula	C27H29N5O3
Molar mass	471.550 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	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 ; Key:VLNHDKDBGWXJEE-GYHUNEDQSA-N ;
	(what is this?) (verify)

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 α_1A-adrenergic receptor (EC₅₀ = 41 nM), and this may contribute to its "severe transient effects".^[6]

References

^ Jones, RM; Portoghese, PS (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 (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.
^ Bruchas, MR; Yang, T; Schreiber, S; Defino, M; Kwan, SC; Li, S; Chavkin, C (2007). "Long-acting κ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ Mague, SD; Pliakas, AM; Todtenkopf, MS; Tomasiewicz, HC; Zhang, Y; Stevens Jr, WC; Jones, RM; Portoghese, PS; Carlezon Jr, WA (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.
^ Obara, I; Mika, J; Schafer, MK; Przewlocka, B (2003). "Antagonists of the κ-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.
^ Porter, James; Munro, Thomas A.; Huang, Xi-Ping; Inglese, Carmela; Perrone, Maria Grazia; Van't Veer, Ashlee; Carroll, F. Ivy; Béguin, Cécile; Carlezon, William A.; Colabufo, Nicola A.; Cohen, Bruce M.; Roth, Bryan L. (2013). "Selective κ Opioid Antagonists nor-BNI, GNTI and JDTic Have Low Affinities for Non-Opioid Receptors and Transporters". PLoS ONE. 8 (8): e70701. doi:10.1371/journal.pone.0070701. ISSN 1932-6203.{{cite journal}}: CS1 maint: unflagged free DOI (link)

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[1] Jones, RM; Portoghese, PS (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 (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.

[3] Bruchas, MR; Yang, T; Schreiber, S; Defino, M; Kwan, SC; Li, S; Chavkin, C (2007). "Long-acting κ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[4] Mague, SD; Pliakas, AM; Todtenkopf, MS; Tomasiewicz, HC; Zhang, Y; Stevens Jr, WC; Jones, RM; Portoghese, PS; Carlezon Jr, WA (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.

[5] Obara, I; Mika, J; Schafer, MK; Przewlocka, B (2003). "Antagonists of the κ-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.

[PorterMunro2013-6] Porter, James; Munro, Thomas A.; Huang, Xi-Ping; Inglese, Carmela; Perrone, Maria Grazia; Van't Veer, Ashlee; Carroll, F. Ivy; Béguin, Cécile; Carlezon, William A.; Colabufo, Nicola A.; Cohen, Bruce M.; Roth, Bryan L. (2013). "Selective κ Opioid Antagonists nor-BNI, GNTI and JDTic Have Low Affinities for Non-Opioid Receptors and Transporters". PLoS ONE. 8 (8): e70701. doi:10.1371/journal.pone.0070701. ISSN 1932-6203.{{cite journal}}: CS1 maint: unflagged free DOI (link)

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See also

References