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Draft:MSX-3

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MSX-3
Identifiers
  • 3-[8-[(E)-2-(3-methoxyphenyl)ethenyl]-7-methyl-2,6-dioxo-1-prop-2-ynylpurin-3-yl]propyl dihydrogen phosphate
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC21H23N4O7P
Molar mass474.410 g·mol−1
3D model (JSmol)
  • CN1C(=NC2=C1C(=O)N(C(=O)N2CCCOP(=O)(O)O)CC#C)/C=C/C3=CC(=CC=C3)OC
  • InChI=1S/C21H23N4O7P/c1-4-11-25-20(26)18-19(24(21(25)27)12-6-13-32-33(28,29)30)22-17(23(18)2)10-9-15-7-5-8-16(14-15)31-3/h1,5,7-10,14H,6,11-13H2,2-3H3,(H2,28,29,30)/b10-9+
  • Key:DUCGTTGSVYZHJS-MDZDMXLPSA-N

MSX-3 is a selective adenosine A2A receptor antagonist.[1][2] Similarly to MSX-4, it is a water-soluble phosphate ester prodrug of MSX-2.[2][3] MSX-3 shows pro-motivational effects in animals.[1][4] Specifically, although it showed no effect on its own, the drug reverses the effort-related deficits induced by the dopamine depleting agent tetrabenazine (TBZ), the dopamine D2 receptor antagonists haloperidol and eticlopride, and the proinflammatory cytokines interleukin-6 and interleukin-1β.[1][4][5][6][7][8] Conversely, it only mildly attenuates the motivational deficits induced by the dopamine D1 receptor antagonist ecopipam (SCH-39166).[5][9]

References

[edit]
  1. ^ a b c Salamone JD, Correa M, Ferrigno S, Yang JH, Rotolo RA, Presby RE (October 2018). "The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine, and Insights into the Neurochemistry of Motivation". Pharmacol Rev. 70 (4): 747–762. doi:10.1124/pr.117.015107. PMC 6169368. PMID 30209181.
  2. ^ a b Müller CE (November 2009). "Prodrug approaches for enhancing the bioavailability of drugs with low solubility". Chem Biodivers. 6 (11): 2071–2083. doi:10.1002/cbdv.200900114. PMID 19937841.
  3. ^ Hauber W, Nagel J, Sauer R, Müller CE (June 1998). "Motor effects induced by a blockade of adenosine A2A receptors in the caudate-putamen". Neuroreport. 9 (8): 1803–1806. doi:10.1097/00001756-199806010-00024. PMID 9665604.
  4. ^ a b López-Cruz L, Salamone JD, Correa M (2018). "Caffeine and Selective Adenosine Receptor Antagonists as New Therapeutic Tools for the Motivational Symptoms of Depression". Front Pharmacol. 9: 526. doi:10.3389/fphar.2018.00526. PMC 5992708. PMID 29910727.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  5. ^ a b Salamone, John D; Correa, Merce; Farrar, Andrew M; Nunes, Eric J; Collins, Lyndsey E (5 May 2010). "Role of dopamine–adenosine interactions in the brain circuitry regulating effort-related decision making: insights into pathological aspects of motivation". Future Neurology. 5 (3): 377–392. doi:10.2217/fnl.10.19. ISSN 1479-6708.
  6. ^ Mott AM, Nunes EJ, Collins LE, Port RG, Sink KS, Hockemeyer J, Müller CE, Salamone JD (May 2009). "The adenosine A2A antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision making in a T-maze cost/benefit procedure". Psychopharmacology (Berl). 204 (1): 103–112. doi:10.1007/s00213-008-1441-z. PMC 2875244. PMID 19132351.
  7. ^ Nunes EJ, Randall PA, Estrada A, Epling B, Hart EE, Lee CA, Baqi Y, Müller CE, Correa M, Salamone JD (February 2014). "Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task". Psychopharmacology (Berl). 231 (4): 727–736. doi:10.1007/s00213-013-3285-4. PMC 4468782. PMID 24136220.
  8. ^ Yohn SE, Arif Y, Haley A, Tripodi G, Baqi Y, Müller CE, Miguel NS, Correa M, Salamone JD (October 2016). "Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6: pharmacological and neurochemical characterization". Psychopharmacology (Berl). 233 (19–20): 3575–3586. doi:10.1007/s00213-016-4392-9. PMID 27497935.
  9. ^ Worden LT, Shahriari M, Farrar AM, Sink KS, Hockemeyer J, Müller CE, Salamone JD (April 2009). "The adenosine A2A antagonist MSX-3 reverses the effort-related effects of dopamine blockade: differential interaction with D1 and D2 family antagonists". Psychopharmacology (Berl). 203 (3): 489–499. doi:10.1007/s00213-008-1396-0. PMC 2875246. PMID 19048234.