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{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc}}
{{Drugbox
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 418106574
| verifiedrevid = 464385140
| IUPAC_name = 1-(2-methylbenzoxazol- 6-yl)- 3-[1,5]naphthyridin- 4-yl urea
| IUPAC_name = 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl urea
| image = SB334867_structure.png
| width = 240px
| image = SB-334,867.svg


<!--Clinical data-->
<!--Clinical data-->
| tradename =
| tradename =
| legal_status =
| legal_status =
| routes_of_administration =
| routes_of_administration =


<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
| metabolism =
| metabolism =
| elimination_half-life =
| elimination_half-life =
| excretion =
| excretion =


<!--Identifiers-->
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 249889-64-3
| CAS_number = 249889-64-3
| PubChem = 6604926
| PubChem = 6604926
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<!--Chemical data-->
<!--Chemical data-->
| C=17 | H=13 | N=5 | O=2
| C=17 | H=13 | N=5 | O=2
| molecular_weight = 319.317 g/mol
| smiles = O=C(Nc1c2ncccc2ncc1)Nc3ccc4nc(oc4c3)C
| smiles = O=C(Nc1c2ncccc2ncc1)Nc3ccc4nc(oc4c3)C
| InChI = 1/C17H13N5O2/c1-10-20-12-5-4-11(9-15(12)24-10)21-17(23)22-14-6-8-18-13-3-2-7-19-16(13)14/h2-9H,1H3,(H2,18,21,22,23)
| InChIKey = AKMNUCBQGHFICM-UHFFFAOYAZ
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C17H13N5O2/c1-10-20-12-5-4-11(9-15(12)24-10)21-17(23)22-14-6-8-18-13-3-2-7-19-16(13)14/h2-9H,1H3,(H2,18,21,22,23)
| StdInChI = 1S/C17H13N5O2/c1-10-20-12-5-4-11(9-15(12)24-10)21-17(23)22-14-6-8-18-13-3-2-7-19-16(13)14/h2-9H,1H3,(H2,18,21,22,23)
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}}
}}


'''SB-334,867''' is an [[orexin antagonist]]. It was the first non-peptide antagonist developed that is selective for the [[orexin receptor]] subtype [[Hypocretin (orexin) receptor 1|OX<sub>1</sub>]], with around 50x selectivity for OX<sub>1</sub> over [[Hypocretin (orexin) receptor 2|OX<sub>2</sub>]] receptors.<ref>{{cite journal | last1 = Smart | first1 = D | last2 = Sabido-David | first2 = C | last3 = Brough | first3 = SJ | last4 = Jewitt | first4 = F | last5 = Johns | first5 = A | last6 = Porter | first6 = RA | last7 = Jerman | first7 = JC | title = SB-334867-A: the first selective orexin-1 receptor antagonist | journal = [[British Journal of Pharmacology]] | volume = 132 | issue = 6 | pages = 1179–82 | year = 2001 | pmid = 11250867 | pmc = 1572677 | doi = 10.1038/sj.bjp.0703953 }}</ref> It has been shown to produce [[sedative]] and [[anorectic]] effects in animals,<ref>{{cite journal | doi = 10.1046/j.0953-816x.2001.01518.x | last1 = Rodgers | first1 = RJ | last2 = Halford | first2 = JC | last3 = Nunes De Souza | first3 = RL | last4 = Canto De Souza | first4 = AL | last5 = Piper | first5 = DC | last6 = Arch | first6 = JR | last7 = Upton | first7 = N | last8 = Porter | first8 = RA | last9 = Johns | first9 = A | title = SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats | journal = The European Journal of Neuroscience | volume = 13 | issue = 7 | pages = 1444–52 | year = 2001 | pmid = 11298806 }}</ref> and has been useful in characterising the orexinergic regulation of brain systems involved with appetite and sleep,<ref>{{cite journal | doi = 10.1016/S0167-0115(01)00358-5 | last1 = Haynes | first1 = AC | last2 = Chapman | first2 = H | last3 = Taylor | first3 = C | last4 = Moore | first4 = GB | last5 = Cawthorne | first5 = MA | last6 = Tadayyon | first6 = M | last7 = Clapham | first7 = JC | last8 = Arch | first8 = JR | title = Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice | journal = Regulatory peptides | volume = 104 | issue = 1–3 | pages = 153–9 | year = 2002 | pmid = 11830290 }}</ref><ref>{{cite journal | last1 = Rodgers | first1 = RJ | last2 = Ishii | first2 = Y | last3 = Halford | first3 = JC | last4 = Blundell | first4 = JE | title = Orexins and appetite regulation | journal = Neuropeptides | volume = 36 | issue = 5 | pages = 303–25 | year = 2002 | pmid = 12450737 | doi=10.1016/S0143-4179(02)00085-9}}</ref><ref>{{cite journal | doi = 10.1046/j.1460-9568.2003.02905.x | last1 = Bernard | first1 = R | last2 = Lydic | first2 = R | last3 = Baghdoyan | first3 = HA | title = Hypocretin-1 causes G protein activation and increases ACh release in rat pons | journal = The European Journal of Neuroscience | volume = 18 | issue = 7 | pages = 1775–85 | year = 2003 | pmid = 14622212 }}</ref><ref>{{cite journal | last1 = Soffin | first1 = EM | last2 = Gill | first2 = CH | last3 = Brough | first3 = SJ | last4 = Jerman | first4 = JC | last5 = Davies | first5 = CH | title = Pharmacological characterisation of the orexin receptor subtype mediating postsynaptic excitation in the rat dorsal raphe nucleus | journal = Neuropharmacology | volume = 46 | issue = 8 | pages = 1168–76 | year = 2004 | pmid = 15111023 | doi = 10.1016/j.neuropharm.2004.02.014 }}</ref><ref>{{cite journal | last1 = Thorpe | first1 = AJ | last2 = Kotz | first2 = CM | title = Orexin a in the nucleus accumbens stimulates feeding and locomotor activity | journal = Brain Research | volume = 1050 | issue = 1–2 | pages = 156–62 | year = 2005 | pmid = 15979595 | doi = 10.1016/j.brainres.2005.05.045 }}</ref><ref>{{cite journal | last1 = Frederick-Duus | first1 = D | last2 = Guyton | first2 = MF | last3 = Fadel | first3 = J | title = Food-elicited increases in cortical acetylcholine release require orexin transmission | journal = Neuroscience | volume = 149 | issue = 3 | pages = 499–507 | year = 2007 | pmid = 17928158 | doi = 10.1016/j.neuroscience.2007.07.061 }}</ref> as well as other physiological processes.<ref>{{cite journal | doi = 10.1210/en.2002-0041 | last1 = Small | first1 = CJ | last2 = Goubillon | first2 = ML | last3 = Murray | first3 = JF | last4 = Siddiqui | first4 = A | last5 = Grimshaw | first5 = SE | last6 = Young | first6 = H | last7 = Sivanesan | first7 = V | last8 = Kalamatianos | first8 = T | last9 = Kennedy | first9 = AR | title = Central orexin a has site-specific effects on luteinizing hormone release in female rats | journal = Endocrinology | volume = 144 | issue = 7 | pages = 3225–36 | year = 2003 | pmid = 12810579 }}</ref><ref>{{cite journal | last1 = D'anna | first1 = KL | last2 = Gammie | first2 = SC | title = Hypocretin-1 dose-dependently modulates maternal behaviour in mice | journal = Journal of neuroendocrinology | volume = 18 | issue = 8 | pages = 553–66 | year = 2006 | pmid = 16867176 | pmc = 2275401 | doi = 10.1111/j.1365-2826.2006.01448.x }}</ref><ref>{{cite journal | last1 = Muschamp | first1 = JW | last2 = Dominguez | first2 = JM | last3 = Sato | first3 = SM | last4 = Shen | first4 = RY | last5 = Hull | first5 = EM | title = A role for hypocretin (orexin) in male sexual behavior | journal = Journal of Neuroscience | volume = 27 | issue = 11 | pages = 2837–45 | year = 2007 | pmid = 17360905 | doi = 10.1523/JNEUROSCI.4121-06.2007 }}</ref><ref>{{cite journal | last1 = Eliassi | first1 = A | last2 = Nazari | first2 = M | last3 = Naghdi | first3 = N | title = Role of the ventromedial hypothalamic orexin-1 receptors in regulation of gastric Acid secretion in conscious rats | journal = Journal of neuroendocrinology | volume = 21 | issue = 3 | pages = 177–82 | year = 2009 | pmid = 19207823 | doi = 10.1111/j.1365-2826.2009.01824.x }}</ref> Orexin antagonists have multiple potential clinical applications including the treatment of drug addiction, insomnia, obesity and diabetes.<ref>{{cite journal | doi = 10.1016/S0014-2999(02)01429-2 | last1 = Smart | first1 = D | last2 = Haynes | first2 = AC | last3 = Williams | first3 = G | last4 = Arch | first4 = JR | title = Orexins and the treatment of obesity | journal = European Journal of Pharmacology | volume = 440 | issue = 2–3 | pages = 199–212 | year = 2002 | pmid = 12007536 }}</ref><ref>{{cite journal | last1 = Bingham | first1 = MJ | last2 = Cai | first2 = J | last3 = Deehan | first3 = MR | title = Eating, sleeping and rewarding: orexin receptors and their antagonists | journal = Current opinion in drug discovery & development | volume = 9 | issue = 5 | pages = 551–9 | year = 2006 | pmid = 17002215 }}</ref><ref>{{cite journal | last1 = Borgland | first1 = SL | last2 = Taha | first2 = SA | last3 = Sarti | first3 = F | last4 = Fields | first4 = HL | last5 = Bonci | first5 = A | title = Orexin a in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine | journal = Neuron | volume = 49 | issue = 4 | pages = 589–601 | year = 2006 | pmid = 16476667 | doi = 10.1016/j.neuron.2006.01.016 }}</ref><ref>{{cite journal | last1 = Narita | first1 = M | last2 = Nagumo | first2 = Y | last3 = Hashimoto | first3 = S | last4 = Narita | first4 = M | last5 = Khotib | first5 = J | last6 = Miyatake | first6 = M | last7 = Sakurai | first7 = T | last8 = Yanagisawa | first8 = M | last9 = Nakamachi | first9 = T | title = Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine | journal = Journal of Neuroscience | volume = 26 | issue = 2 | pages = 398–405 | year = 2006 | pmid = 16407535 | doi = 10.1523/JNEUROSCI.2761-05.2006 }}</ref><ref>{{cite journal | last1 = Lawrence | first1 = AJ | last2 = Cowen | first2 = MS | last3 = Yang | first3 = HJ | last4 = Chen | first4 = F | last5 = Oldfield | first5 = B | title = The orexin system regulates alcohol-seeking in rats | journal = British Journal of Pharmacology | volume = 148 | issue = 6 | pages = 752–9 | year = 2006 | pmid = 16751790 | pmc = 1617074 | doi = 10.1038/sj.bjp.0706789 }}</ref><ref>{{cite journal | last1 = Sharf | first1 = R | last2 = Sarhan | first2 = M | last3 = Dileone | first3 = RJ | title = Orexin Mediates the Expression of Precipitated Morphine Withdrawal and Concurrent Activation of the Nucleus Accumbens Shell | journal = Biological Psychiatry | volume = 64 | issue = 3 | pages = 175–83 | year = 2008 | pmid = 18423425 | pmc = 2529153 | doi = 10.1016/j.biopsych.2008.03.006 }}</ref><ref>{{cite journal | last1 = Aston-Jones | first1 = G | last2 = Smith | first2 = RJ | last3 = Moorman | first3 = DE | last4 = Richardson | first4 = KA | title = Role of lateral hypothalamic orexin neurons in reward processing and addiction | journal = Neuropharmacology | volume = 56 Suppl 1 | pages = 112–21 | year = 2009 | pmid = 18655797 | pmc = 2635332 | doi = 10.1016/j.neuropharm.2008.06.060 | issue = Suppl 1 }}</ref> <ref>{{cite journal|last=Martin-Fardon|first=R|coauthors=et al|title=Blockade of hypocretin receptor-1 preferentially prevents cocaine seeking: comparison with natural reward seeking.|journal=Neuroreport. (2014)}}</ref>
'''SB-334867''' is an [[orexin antagonist]]. It was the first non-peptide antagonist developed that is selective for the [[orexin receptor]] subtype [[Hypocretin (orexin) receptor 1|OX<sub>1</sub>]], with around 50x selectivity for OX<sub>1</sub> over [[Hypocretin (orexin) receptor 2|OX<sub>2</sub>]] receptors.<ref>{{cite journal | vauthors = Smart D, Sabido-David C, Brough SJ, Jewitt F, Johns A, Porter RA, Jerman JC | title = SB-334867-A: the first selective orexin-1 receptor antagonist | journal = British Journal of Pharmacology | volume = 132 | issue = 6 | pages = 1179–82 | date = March 2001 | pmid = 11250867 | pmc = 1572677 | doi = 10.1038/sj.bjp.0703953 }}</ref> It has been shown to produce [[sedative]] and [[anorectic]] effects in animals,<ref>{{cite journal | vauthors = Rodgers RJ, Halford JC, Nunes de Souza RL, Canto de Souza AL, Piper DC, Arch JR, Upton N, Porter RA, Johns A, Blundell JE | display-authors = 6 | title = SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats | journal = The European Journal of Neuroscience | volume = 13 | issue = 7 | pages = 1444–52 | date = April 2001 | pmid = 11298806 | doi = 10.1046/j.0953-816x.2001.01518.x | s2cid = 24935644 }}</ref> and has been useful in characterising the orexinergic regulation of brain systems involved with appetite and sleep,<ref>{{cite journal | vauthors = Haynes AC, Chapman H, Taylor C, Moore GB, Cawthorne MA, Tadayyon M, Clapham JC, Arch JR | display-authors = 6 | title = Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice | journal = Regulatory Peptides | volume = 104 | issue = 1–3 | pages = 153–9 | date = March 2002 | pmid = 11830290 | doi = 10.1016/S0167-0115(01)00358-5 | s2cid = 25523175 }}</ref><ref>{{cite journal | vauthors = Rodgers RJ, Ishii Y, Halford JC, Blundell JE | title = Orexins and appetite regulation | journal = Neuropeptides | volume = 36 | issue = 5 | pages = 303–25 | date = October 2002 | pmid = 12450737 | doi = 10.1016/S0143-4179(02)00085-9 | s2cid = 23352886 }}</ref><ref>{{cite journal | vauthors = Bernard R, Lydic R, Baghdoyan HA | title = Hypocretin-1 causes G protein activation and increases ACh release in rat pons | journal = The European Journal of Neuroscience | volume = 18 | issue = 7 | pages = 1775–85 | date = October 2003 | pmid = 14622212 | doi = 10.1046/j.1460-9568.2003.02905.x | url = https://deepblue.lib.umich.edu/bitstream/2027.42/75751/1/j.1460-9568.2003.02905.x.pdf | hdl = 2027.42/75751 | s2cid = 18515164 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Soffin EM, Gill CH, Brough SJ, Jerman JC, Davies CH | title = Pharmacological characterisation of the orexin receptor subtype mediating postsynaptic excitation in the rat dorsal raphe nucleus | journal = Neuropharmacology | volume = 46 | issue = 8 | pages = 1168–76 | date = June 2004 | pmid = 15111023 | doi = 10.1016/j.neuropharm.2004.02.014 | s2cid = 45872346 }}</ref><ref>{{cite journal | vauthors = Thorpe AJ, Kotz CM | title = Orexin A in the nucleus accumbens stimulates feeding and locomotor activity | journal = Brain Research | volume = 1050 | issue = 1–2 | pages = 156–62 | date = July 2005 | pmid = 15979595 | doi = 10.1016/j.brainres.2005.05.045 | s2cid = 24662237 }}</ref><ref>{{cite journal | vauthors = Frederick-Duus D, Guyton MF, Fadel J | title = Food-elicited increases in cortical acetylcholine release require orexin transmission | journal = Neuroscience | volume = 149 | issue = 3 | pages = 499–507 | date = November 2007 | pmid = 17928158 | doi = 10.1016/j.neuroscience.2007.07.061 | s2cid = 19452926 }}</ref> as well as other physiological processes.<ref>{{cite journal | vauthors = Small CJ, Goubillon ML, Murray JF, Siddiqui A, Grimshaw SE, Young H, Sivanesan V, Kalamatianos T, Kennedy AR, Coen CW, Bloom SR, Wilson CA | display-authors = 6 | title = Central orexin A has site-specific effects on luteinizing hormone release in female rats | journal = Endocrinology | volume = 144 | issue = 7 | pages = 3225–36 | date = July 2003 | pmid = 12810579 | doi = 10.1210/en.2002-0041 | doi-access = free }}</ref><ref>{{cite journal | vauthors = D'Anna KL, Gammie SC | title = Hypocretin-1 dose-dependently modulates maternal behaviour in mice | journal = Journal of Neuroendocrinology | volume = 18 | issue = 8 | pages = 553–66 | date = August 2006 | pmid = 16867176 | pmc = 2275401 | doi = 10.1111/j.1365-2826.2006.01448.x }}</ref><ref>{{cite journal | vauthors = Muschamp JW, Dominguez JM, Sato SM, Shen RY, Hull EM | title = A role for hypocretin (orexin) in male sexual behavior | journal = The Journal of Neuroscience | volume = 27 | issue = 11 | pages = 2837–45 | date = March 2007 | pmid = 17360905 | pmc = 6672590 | doi = 10.1523/JNEUROSCI.4121-06.2007 }}</ref><ref>{{cite journal | vauthors = Eliassi A, Nazari M, Naghdi N | title = Role of the ventromedial hypothalamic orexin-1 receptors in regulation of gastric Acid secretion in conscious rats | journal = Journal of Neuroendocrinology | volume = 21 | issue = 3 | pages = 177–82 | date = March 2009 | pmid = 19207823 | doi = 10.1111/j.1365-2826.2009.01824.x | s2cid = 23781282 }}</ref> The hydrochloride salt of SB-334867 has been demonstrated to be hydrolytically unstable, both in solution and as the solid.<ref>{{cite journal | vauthors = McElhinny CJ, Lewin AH, Mascarella SW, Runyon S, Brieaddy L, Carroll FI | title = Hydrolytic instability of the important orexin 1 receptor antagonist SB-334867: possible confounding effects on in vivo and in vitro studies | journal = Bioorganic & Medicinal Chemistry Letters | volume = 22 | issue = 21 | pages = 6661–4 | date = November 2012 | pmid = 23031594 | doi = 10.1016/j.bmcl.2012.08.109 }}</ref> Orexin antagonists have multiple potential clinical applications including the treatment of drug addiction, insomnia, obesity and diabetes.<ref>{{cite journal | vauthors = Smart D, Haynes AC, Williams G, Arch JR | title = Orexins and the treatment of obesity | journal = European Journal of Pharmacology | volume = 440 | issue = 2–3 | pages = 199–212 | date = April 2002 | pmid = 12007536 | doi = 10.1016/S0014-2999(02)01429-2 }}</ref><ref>{{cite journal | vauthors = Bingham MJ, Cai J, Deehan MR | title = Eating, sleeping and rewarding: orexin receptors and their antagonists | journal = Current Opinion in Drug Discovery & Development | volume = 9 | issue = 5 | pages = 551–9 | date = September 2006 | pmid = 17002215 }}</ref><ref>{{cite journal | vauthors = Borgland SL, Taha SA, Sarti F, Fields HL, Bonci A | title = Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine | journal = Neuron | volume = 49 | issue = 4 | pages = 589–601 | date = February 2006 | pmid = 16476667 | doi = 10.1016/j.neuron.2006.01.016 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Narita M, Nagumo Y, Hashimoto S, Narita M, Khotib J, Miyatake M, Sakurai T, Yanagisawa M, Nakamachi T, Shioda S, Suzuki T | display-authors = 6 | title = Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine | journal = The Journal of Neuroscience | volume = 26 | issue = 2 | pages = 398–405 | date = January 2006 | pmid = 16407535 | pmc = 6674410 | doi = 10.1523/JNEUROSCI.2761-05.2006 }}</ref><ref>{{cite journal | vauthors = Lawrence AJ, Cowen MS, Yang HJ, Chen F, Oldfield B | title = The orexin system regulates alcohol-seeking in rats | journal = British Journal of Pharmacology | volume = 148 | issue = 6 | pages = 752–9 | date = July 2006 | pmid = 16751790 | pmc = 1617074 | doi = 10.1038/sj.bjp.0706789 }}</ref><ref>{{cite journal | vauthors = Sharf R, Sarhan M, Dileone RJ | title = Orexin mediates the expression of precipitated morphine withdrawal and concurrent activation of the nucleus accumbens shell | journal = Biological Psychiatry | volume = 64 | issue = 3 | pages = 175–83 | date = August 2008 | pmid = 18423425 | pmc = 2529153 | doi = 10.1016/j.biopsych.2008.03.006 }}</ref><ref>{{cite journal | vauthors = Aston-Jones G, Smith RJ, Moorman DE, Richardson KA | title = Role of lateral hypothalamic orexin neurons in reward processing and addiction | journal = Neuropharmacology | volume = 56 | issue = Suppl 1 | pages = 112–21 | year = 2009 | pmid = 18655797 | pmc = 2635332 | doi = 10.1016/j.neuropharm.2008.06.060 }}</ref><ref>{{cite journal | vauthors = Martin-Fardon R, Weiss F | title = Blockade of hypocretin receptor-1 preferentially prevents cocaine seeking: comparison with natural reward seeking | journal = NeuroReport | volume = 25 | issue = 7 | pages = 485–8 | date = May 2014 | pmid = 24407199 | pmc = 3981907 | doi = 10.1097/wnr.0000000000000120 }}</ref>


==References==
== References ==
{{reflist}}
{{reflist}}


{{Hypnotics and sedatives}}
{{Hypnotics and sedatives}}
{{Orexin receptor modulators}}
{{Neuropeptide agonists and antagonists}}


[[Category:Sedatives]]
[[Category:Sedatives]]
Line 50: Line 49:
[[Category:Naphthyridines]]
[[Category:Naphthyridines]]
[[Category:Ureas]]
[[Category:Ureas]]



{{sedative-stub}}
{{sedative-stub}}

Latest revision as of 21:32, 22 January 2024

SB-334867
Identifiers
  • 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl urea
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.164.490 Edit this at Wikidata
Chemical and physical data
FormulaC17H13N5O2
Molar mass319.324 g·mol−1
3D model (JSmol)
  • O=C(Nc1c2ncccc2ncc1)Nc3ccc4nc(oc4c3)C
  • InChI=1S/C17H13N5O2/c1-10-20-12-5-4-11(9-15(12)24-10)21-17(23)22-14-6-8-18-13-3-2-7-19-16(13)14/h2-9H,1H3,(H2,18,21,22,23) checkY
  • Key:AKMNUCBQGHFICM-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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]

References

[edit]
  1. ^ Smart D, Sabido-David C, Brough SJ, Jewitt F, Johns A, Porter RA, Jerman JC (March 2001). "SB-334867-A: the first selective orexin-1 receptor antagonist". British Journal of Pharmacology. 132 (6): 1179–82. doi:10.1038/sj.bjp.0703953. PMC 1572677. PMID 11250867.
  2. ^ Rodgers RJ, Halford JC, Nunes de Souza RL, Canto de Souza AL, Piper DC, Arch JR, et al. (April 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. doi:10.1046/j.0953-816x.2001.01518.x. PMID 11298806. S2CID 24935644.
  3. ^ Haynes AC, Chapman H, Taylor C, Moore GB, Cawthorne MA, Tadayyon M, et al. (March 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. doi:10.1016/S0167-0115(01)00358-5. PMID 11830290. S2CID 25523175.
  4. ^ Rodgers RJ, Ishii Y, Halford JC, Blundell JE (October 2002). "Orexins and appetite regulation". Neuropeptides. 36 (5): 303–25. doi:10.1016/S0143-4179(02)00085-9. PMID 12450737. S2CID 23352886.
  5. ^ Bernard R, Lydic R, Baghdoyan HA (October 2003). "Hypocretin-1 causes G protein activation and increases ACh release in rat pons" (PDF). The European Journal of Neuroscience. 18 (7): 1775–85. doi:10.1046/j.1460-9568.2003.02905.x. hdl:2027.42/75751. PMID 14622212. S2CID 18515164.
  6. ^ Soffin EM, Gill CH, Brough SJ, Jerman JC, Davies CH (June 2004). "Pharmacological characterisation of the orexin receptor subtype mediating postsynaptic excitation in the rat dorsal raphe nucleus". Neuropharmacology. 46 (8): 1168–76. doi:10.1016/j.neuropharm.2004.02.014. PMID 15111023. S2CID 45872346.
  7. ^ Thorpe AJ, Kotz CM (July 2005). "Orexin A in the nucleus accumbens stimulates feeding and locomotor activity". Brain Research. 1050 (1–2): 156–62. doi:10.1016/j.brainres.2005.05.045. PMID 15979595. S2CID 24662237.
  8. ^ Frederick-Duus D, Guyton MF, Fadel J (November 2007). "Food-elicited increases in cortical acetylcholine release require orexin transmission". Neuroscience. 149 (3): 499–507. doi:10.1016/j.neuroscience.2007.07.061. PMID 17928158. S2CID 19452926.
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