SB-334867 explained

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] The hydrochloride salt of SB-334867 has been demonstrated to be hydrolytically unstable, both in solution and as the solid.[13] Orexin antagonists have multiple potential clinical applications including the treatment of drug addiction, insomnia, obesity and diabetes.[14] [15] [16] [17] [18] [19] [20] [21]

Notes and References

  1. Smart D, Sabido-David C, Brough SJ, Jewitt F, Johns A, Porter RA, Jerman JC . SB-334867-A: the first selective orexin-1 receptor antagonist . British Journal of Pharmacology . 132 . 6 . 1179–82 . March 2001 . 11250867 . 1572677 . 10.1038/sj.bjp.0703953 .
  2. Rodgers RJ, Halford JC, Nunes de Souza RL, Canto de Souza AL, Piper DC, Arch JR, Upton N, Porter RA, Johns A, Blundell JE . 6 . 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 . April 2001 . 11298806 . 10.1046/j.0953-816x.2001.01518.x . 24935644 .
  3. Haynes AC, Chapman H, Taylor C, Moore GB, Cawthorne MA, Tadayyon M, Clapham JC, Arch JR . 6 . Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice . Regulatory Peptides . 104 . 1–3 . 153–9 . March 2002 . 11830290 . 10.1016/S0167-0115(01)00358-5 . 25523175 .
  4. Rodgers RJ, Ishii Y, Halford JC, Blundell JE . Orexins and appetite regulation . Neuropeptides . 36 . 5 . 303–25 . October 2002 . 12450737 . 10.1016/S0143-4179(02)00085-9 . 23352886 .
  5. Bernard R, Lydic R, Baghdoyan HA . Hypocretin-1 causes G protein activation and increases ACh release in rat pons . The European Journal of Neuroscience . 18 . 7 . 1775–85 . October 2003 . 14622212 . 10.1046/j.1460-9568.2003.02905.x . 2027.42/75751 . 18515164 . free .
  6. Soffin EM, Gill CH, Brough SJ, Jerman JC, Davies CH . Pharmacological characterisation of the orexin receptor subtype mediating postsynaptic excitation in the rat dorsal raphe nucleus . Neuropharmacology . 46 . 8 . 1168–76 . June 2004 . 15111023 . 10.1016/j.neuropharm.2004.02.014 . 45872346 .
  7. Thorpe AJ, Kotz CM . Orexin A in the nucleus accumbens stimulates feeding and locomotor activity . Brain Research . 1050 . 1–2 . 156–62 . July 2005 . 15979595 . 10.1016/j.brainres.2005.05.045 . 24662237 .
  8. Frederick-Duus D, Guyton MF, Fadel J . Food-elicited increases in cortical acetylcholine release require orexin transmission . Neuroscience . 149 . 3 . 499–507 . November 2007 . 17928158 . 10.1016/j.neuroscience.2007.07.061 . 19452926 .
  9. Small CJ, Goubillon ML, Murray JF, Siddiqui A, Grimshaw SE, Young H, Sivanesan V, Kalamatianos T, Kennedy AR, Coen CW, Bloom SR, Wilson CA . 6 . Central orexin A has site-specific effects on luteinizing hormone release in female rats . Endocrinology . 144 . 7 . 3225–36 . July 2003 . 12810579 . 10.1210/en.2002-0041 . free .
  10. D'Anna KL, Gammie SC . Hypocretin-1 dose-dependently modulates maternal behaviour in mice . Journal of Neuroendocrinology . 18 . 8 . 553–66 . August 2006 . 16867176 . 2275401 . 10.1111/j.1365-2826.2006.01448.x .
  11. Muschamp JW, Dominguez JM, Sato SM, Shen RY, Hull EM . A role for hypocretin (orexin) in male sexual behavior . The Journal of Neuroscience . 27 . 11 . 2837–45 . March 2007 . 17360905 . 6672590 . 10.1523/JNEUROSCI.4121-06.2007 .
  12. Eliassi A, Nazari M, Naghdi N . Role of the ventromedial hypothalamic orexin-1 receptors in regulation of gastric Acid secretion in conscious rats . Journal of Neuroendocrinology . 21 . 3 . 177–82 . March 2009 . 19207823 . 10.1111/j.1365-2826.2009.01824.x . 23781282 .
  13. McElhinny CJ, Lewin AH, Mascarella SW, Runyon S, Brieaddy L, Carroll FI . Hydrolytic instability of the important orexin 1 receptor antagonist SB-334867: possible confounding effects on in vivo and in vitro studies . Bioorganic & Medicinal Chemistry Letters . 22 . 21 . 6661–4 . November 2012 . 23031594 . 10.1016/j.bmcl.2012.08.109 .
  14. Smart D, Haynes AC, Williams G, Arch JR . Orexins and the treatment of obesity . European Journal of Pharmacology . 440 . 2–3 . 199–212 . April 2002 . 12007536 . 10.1016/S0014-2999(02)01429-2 .
  15. Bingham MJ, Cai J, Deehan MR . Eating, sleeping and rewarding: orexin receptors and their antagonists . Current Opinion in Drug Discovery & Development . 9 . 5 . 551–9 . September 2006 . 17002215 .
  16. Borgland SL, Taha SA, Sarti F, Fields HL, Bonci A . Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine . Neuron . 49 . 4 . 589–601 . February 2006 . 16476667 . 10.1016/j.neuron.2006.01.016 . free .
  17. Narita M, Nagumo Y, Hashimoto S, Narita M, Khotib J, Miyatake M, Sakurai T, Yanagisawa M, Nakamachi T, Shioda S, Suzuki T . 6 . Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine . The Journal of Neuroscience . 26 . 2 . 398–405 . January 2006 . 16407535 . 6674410 . 10.1523/JNEUROSCI.2761-05.2006 .
  18. Lawrence AJ, Cowen MS, Yang HJ, Chen F, Oldfield B . The orexin system regulates alcohol-seeking in rats . British Journal of Pharmacology . 148 . 6 . 752–9 . July 2006 . 16751790 . 1617074 . 10.1038/sj.bjp.0706789 .
  19. Sharf R, Sarhan M, Dileone RJ . Orexin mediates the expression of precipitated morphine withdrawal and concurrent activation of the nucleus accumbens shell . Biological Psychiatry . 64 . 3 . 175–83 . August 2008 . 18423425 . 2529153 . 10.1016/j.biopsych.2008.03.006 .
  20. Aston-Jones G, Smith RJ, Moorman DE, Richardson KA . Role of lateral hypothalamic orexin neurons in reward processing and addiction . Neuropharmacology . 56 . Suppl 1 . 112–21 . 2009 . 18655797 . 2635332 . 10.1016/j.neuropharm.2008.06.060 .
  21. Martin-Fardon R, Weiss F . Blockade of hypocretin receptor-1 preferentially prevents cocaine seeking: comparison with natural reward seeking . NeuroReport . 25 . 7 . 485–8 . May 2014 . 24407199 . 3981907 . 10.1097/wnr.0000000000000120 .

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