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Sb-334,867

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Title: Sb-334,867  
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Sb-334,867

SB-334,867
Systematic (IUPAC) name
1-(2-methylbenzoxazol- 6-yl)- 3-[1,5]naphthyridin- 4-yl urea
Clinical data
Legal status
?
Identifiers
CAS number  N
ATC code ?
PubChem
IUPHAR ligand
ChemSpider  YesY
ChEMBL  YesY
Chemical data
Formula C17H13N5O2 
Mol. mass 319.317 g/mol
 N   

SB-334867 is an orexin antagonist. It was the first non-peptide antagonist developed that is selective for the orexin receptor subtype OX1, with around 50x selectivity for OX1 over OX2 receptors.[1] It has been shown to produce sedative and anorectic effects in animals,[2] and has been useful in characterising the orexinergic regulation of brain systems involved with appetite and sleep,[3][4][5][6][7][8] as well as other physiological processes.[9][10][11][12] Orexin antagonists have multiple potential clinical applications including the treatment of drug addiction, insomnia, obesity and diabetes.[13][14][15][16][17][18][19][20]

References

  1. ^ Smart, D; Sabido-David, C; Brough, SJ; Jewitt, F; Johns, A; Porter, RA; Jerman, JC (2001). "SB-334867-A: the first selective orexin-1 receptor antagonist".  
  2. ^ Rodgers, RJ; Halford, JC; Nunes De Souza, RL; Canto De Souza, AL; Piper, DC; Arch, JR; Upton, N; Porter, RA; Johns, A (2001). "SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats". The European Journal of Neuroscience 13 (7): 1444–52.  
  3. ^ Haynes, AC; Chapman, H; Taylor, C; Moore, GB; Cawthorne, MA; Tadayyon, M; Clapham, JC; Arch, JR (2002). "Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice". Regulatory peptides 104 (1–3): 153–9.  
  4. ^ Rodgers, RJ; Ishii, Y; Halford, JC; Blundell, JE (2002). "Orexins and appetite regulation". Neuropeptides 36 (5): 303–25.  
  5. ^ Bernard, R; Lydic, R; Baghdoyan, HA (2003). "Hypocretin-1 causes G protein activation and increases ACh release in rat pons". The European Journal of Neuroscience 18 (7): 1775–85.  
  6. ^ Soffin, EM; Gill, CH; Brough, SJ; Jerman, JC; Davies, CH (2004). "Pharmacological characterisation of the orexin receptor subtype mediating postsynaptic excitation in the rat dorsal raphe nucleus". Neuropharmacology 46 (8): 1168–76.  
  7. ^ Thorpe, AJ; Kotz, CM (2005). "Orexin a in the nucleus accumbens stimulates feeding and locomotor activity". Brain Research 1050 (1–2): 156–62.  
  8. ^ Frederick-Duus, D; Guyton, MF; Fadel, J (2007). "Food-elicited increases in cortical acetylcholine release require orexin transmission". Neuroscience 149 (3): 499–507.  
  9. ^ Small, CJ; Goubillon, ML; Murray, JF; Siddiqui, A; Grimshaw, SE; Young, H; Sivanesan, V; Kalamatianos, T; Kennedy, AR (2003). "Central orexin a has site-specific effects on luteinizing hormone release in female rats". Endocrinology 144 (7): 3225–36.  
  10. ^ D'anna, KL; Gammie, SC (2006). "Hypocretin-1 dose-dependently modulates maternal behaviour in mice". Journal of neuroendocrinology 18 (8): 553–66.  
  11. ^ Muschamp, JW; Dominguez, JM; Sato, SM; Shen, RY; Hull, EM (2007). "A role for hypocretin (orexin) in male sexual behavior". Journal of Neuroscience 27 (11): 2837–45.  
  12. ^ Eliassi, A; Nazari, M; Naghdi, N (2009). "Role of the ventromedial hypothalamic orexin-1 receptors in regulation of gastric Acid secretion in conscious rats". Journal of neuroendocrinology 21 (3): 177–82.  
  13. ^ Smart, D; Haynes, AC; Williams, G; Arch, JR (2002). "Orexins and the treatment of obesity". European Journal of Pharmacology 440 (2–3): 199–212.  
  14. ^ Bingham, MJ; Cai, J; Deehan, MR (2006). "Eating, sleeping and rewarding: orexin receptors and their antagonists". Current opinion in drug discovery & development 9 (5): 551–9.  
  15. ^ Borgland, SL; Taha, SA; Sarti, F; Fields, HL; Bonci, A (2006). "Orexin a in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine". Neuron 49 (4): 589–601.  
  16. ^ Narita, M; Nagumo, Y; Hashimoto, S; Narita, M; Khotib, J; Miyatake, M; Sakurai, T; Yanagisawa, M; Nakamachi, T (2006). "Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine". Journal of Neuroscience 26 (2): 398–405.  
  17. ^ Lawrence, AJ; Cowen, MS; Yang, HJ; Chen, F; Oldfield, B (2006). "The orexin system regulates alcohol-seeking in rats". British Journal of Pharmacology 148 (6): 752–9.  
  18. ^ Sharf, R; Sarhan, M; Dileone, RJ (2008). "Orexin Mediates the Expression of Precipitated Morphine Withdrawal and Concurrent Activation of the Nucleus Accumbens Shell". Biological Psychiatry 64 (3): 175–83.  
  19. ^ Aston-Jones, G; Smith, RJ; Moorman, DE; Richardson, KA (2009). "Role of lateral hypothalamic orexin neurons in reward processing and addiction". Neuropharmacology. 56 Suppl 1 (Suppl 1): 112–21.  
  20. ^ Martin-Fardon, R; et al (2014). "Blockade of hypocretin receptor-1 preferentially prevents cocaine seeking: comparison with natural reward seeking". NeuroReport.  


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