SB-277,011-A

SB-277,011-A
Identifiers
IUPAC name
  • N-{trans-4-[2-(6-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl]cyclohexyl}quinoline-4-carboxamide
PubChem CID
IUPHAR/BPS
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC28H30N4O
Molar mass438.575 g·mol−1
3D model (JSmol)
SMILES
  • c4cccc1c4nccc1C(=O)NC3CCC(CC3)CCN(CCc2c5)Cc2ccc5C#N
InChI
  • InChI=1S/C28H30N4O/c29-18-21-5-8-23-19-32(16-13-22(23)17-21)15-12-20-6-9-24(10-7-20)31-28(33)26-11-14-30-27-4-2-1-3-25(26)27/h1-5,8,11,14,17,20,24H,6-7,9-10,12-13,15-16,19H2,(H,31,33) ☒N
  • Key:OLWRVVHPJFLNPW-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

SB-277,011A is a drug which acts as a potent and selective dopamine D3 receptor antagonist,[1] which is around 80-100x selective for D3 over D2,[2] and lacks any partial agonist activity.[3]

SB-277,011A is used in the study of addiction to stimulant drugs such as nicotine[4] and cocaine.[5][6] Where cocaine reduces the threshold for brain electrical self-stimulation in rats, an indication of cocaine's rewarding effects, SB-277,011A completely reverses this effect. It may thus be useful in the treatment of addiction to nicotine and cocaine,[7][8][9] and is also being investigated for potential uses in the treatment of other drug addictions, such as addiction to heroin[10] and alcohol.[11][12][13]

Another potential application for SB-277,011A is in the treatment of schizophrenia,[14] and it may be particularly useful in treating comorbid patients who are both schizophrenic and addicted to drugs.[15] However it may worsen side effects such as tardive dyskinesia in patients who are already prescribed antipsychotic drugs.[16]

References

  1. ↑ Stemp G, Ashmeade T, Branch CL, Hadley MS, Hunter AJ, Johnson CN, et al. (May 2000). "Design and synthesis of trans-N-[4-[2-(6-cyano-1,2,3, 4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide (SB-277011): A potent and selective dopamine D(3) receptor antagonist with high oral bioavailability and CNS penetration in the rat". Journal of Medicinal Chemistry. 43 (9): 1878–85. doi:10.1021/jm000090i. PMID 10794704.
  2. ↑ Southam E, Lloyd A, Jennings CA, Cluderay JE, Cilia J, Gartlon JE, Jones DN (May 2007). "Effect of the selective dopamine D3 receptor antagonist SB-277011-A on regional c-Fos-like expression in rat forebrain". Brain Research. 1149: 50–7. doi:10.1016/j.brainres.2007.02.051. PMID 17382304. S2CID 12557234.
  3. ↑ Reavill C, Taylor SG, Wood MD, Ashmeade T, Austin NE, Avenell KY, et al. (September 2000). "Pharmacological actions of a novel, high-affinity, and selective human dopamine D(3) receptor antagonist, SB-277011-A". The Journal of Pharmacology and Experimental Therapeutics. 294 (3): 1154–65. PMID 10945872.
  4. ↑ Le Foll B, Schwartz JC, Sokoloff P (February 2003). "Disruption of nicotine conditioning by dopamine D(3) receptor ligands". Molecular Psychiatry. 8 (2): 225–30. doi:10.1038/sj.mp.4001202. PMID 12610655.
  5. ↑ Vorel SR, Ashby CR, Paul M, Liu X, Hayes R, Hagan JJ, et al. (November 2002). "Dopamine D3 receptor antagonism inhibits cocaine-seeking and cocaine-enhanced brain reward in rats". The Journal of Neuroscience. 22 (21): 9595–603. doi:10.1523/JNEUROSCI.22-21-09595.2002. PMC 6758043. PMID 12417684.
  6. ↑ Di Ciano P, Underwood RJ, Hagan JJ, Everitt BJ (February 2003). "Attenuation of cue-controlled cocaine-seeking by a selective D3 dopamine receptor antagonist SB-277011-A". Neuropsychopharmacology. 28 (2): 329–38. doi:10.1038/sj.npp.1300148. PMID 12589386.
  7. ↑ Andreoli M, Tessari M, Pilla M, Valerio E, Hagan JJ, Heidbreder CA (July 2003). "Selective antagonism at dopamine D3 receptors prevents nicotine-triggered relapse to nicotine-seeking behavior". Neuropsychopharmacology. 28 (7): 1272–80. doi:10.1038/sj.npp.1300183. PMID 12700694.
  8. ↑ Ross JT, Corrigall WA, Heidbreder CA, LeSage MG (March 2007). "Effects of the selective dopamine D3 receptor antagonist SB-277011A on the reinforcing effects of nicotine as measured by a progressive-ratio schedule in rats". European Journal of Pharmacology. 559 (2–3): 173–9. doi:10.1016/j.ejphar.2007.01.004. PMID 17303116.
  9. ↑ Xi ZX, Gilbert J, Campos AC, Kline N, Ashby CR, Hagan JJ, et al. (October 2004). "Blockade of mesolimbic dopamine D3 receptors inhibits stress-induced reinstatement of cocaine-seeking in rats". Psychopharmacology. 176 (1): 57–65. doi:10.1007/s00213-004-1858-y. PMC 3726040. PMID 15083257.
  10. ↑ Ashby CR, Paul M, Gardner EL, Heidbreder CA, Hagan JJ (June 2003). "Acute administration of the selective D3 receptor antagonist SB-277011A blocks the acquisition and expression of the conditioned place preference response to heroin in male rats". Synapse. 48 (3): 154–6. doi:10.1002/syn.10188. PMID 12645041. S2CID 26458149.
  11. ↑ Thanos PK, Katana JM, Ashby CR, Michaelides M, Gardner EL, Heidbreder CA, Volkow ND (May 2005). "The selective dopamine D3 receptor antagonist SB-277011-A attenuates ethanol consumption in ethanol preferring (P) and non-preferring (NP) rats". Pharmacology, Biochemistry, and Behavior. 81 (1): 190–7. doi:10.1016/j.pbb.2005.03.013. PMID 15894078. S2CID 15406751.
  12. ↑ Vengeliene V, Leonardi-Essmann F, Perreau-Lenz S, Gebicke-Haerter P, Drescher K, Gross G, Spanagel R (November 2006). "The dopamine D3 receptor plays an essential role in alcohol-seeking and relapse". FASEB Journal. 20 (13): 2223–33. doi:10.1096/fj.06-6110com. PMID 17077299. S2CID 9431585.
  13. ↑ Heidbreder CA, Andreoli M, Marcon C, Hutcheson DM, Gardner EL, Ashby CR (March 2007). "Evidence for the role of dopamine D3 receptors in oral operant alcohol self-administration and reinstatement of alcohol-seeking behavior in mice". Addiction Biology. 12 (1): 35–50. doi:10.1111/j.1369-1600.2007.00051.x. PMID 17407496. S2CID 25984106.
  14. ↑ Joyce JN, Millan MJ (July 2005). "Dopamine D3 receptor antagonists as therapeutic agents". Drug Discovery Today. 10 (13): 917–25. doi:10.1016/S1359-6446(05)03491-4. PMID 15993811.
  15. ↑ Jahnke U (January 2008). "Experimental pharmacotherapeutics for schizophrenia and addiction". IDrugs. 11 (1): 7–9. PMID 18175251.
  16. ↑ Malik P, Andersen MB, Peacock L (August 2004). "The effects of dopamine D3 agonists and antagonists in a nonhuman primate model of tardive dyskinesia". Pharmacology, Biochemistry, and Behavior. 78 (4): 805–10. doi:10.1016/j.pbb.2004.05.019. PMID 15301939. S2CID 19410897.
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