MSX-2

The topic of MSX-2 has been the subject of interest and debate for a long time. From its origins to the present day, MSX-2 has played a significant role in various aspects of society. In order to better understand this topic, it is essential to delve into its history, its implications and its impact in different contexts. In this article, different perspectives on MSX-2 will be addressed, with the purpose of offering a comprehensive vision that allows readers to acquire a more complete and enriching understanding of this topic.

Not to be confused with MSX2.
MSX-2
Clinical data
Other names3-(3-Hydroxypropyl)-7-methyl-8-(3-methoxystyryl)-1-propargylxanthine
Drug classAdenosine A2A receptor antagonist
Identifiers
  • 3-(3-hydroxypropyl)-8--7-methyl-1-prop-2-ynylpurine-2,6-dione
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H22N4O4
Molar mass394.431 g·mol−1
3D model (JSmol)
  • CN1C(=NC2=C1C(=O)N(C(=O)N2CCCO)CC#C)/C=C/C3=CC(=CC=C3)OC
  • InChI=1S/C21H22N4O4/c1-4-11-25-20(27)18-19(24(21(25)28)12-6-13-26)22-17(23(18)2)10-9-15-7-5-8-16(14-15)29-3/h1,5,7-10,14,26H,6,11-13H2,2-3H3/b10-9+
  • Key:FWLDDFYHEQMIGG-MDZDMXLPSA-N

MSX-2 is a selective adenosine A2A receptor antagonist used in scientific research.[1] It is a xanthine and a derivative of the non-selective adenosine receptor antagonist caffeine.[1][2]

The affinities (Ki) of MSX-2 for the human adenosine receptors are 5.38 to 14.5 nM for the adenosine A2A receptor, 2,500 nM for the adenosine A1 receptor (172- to 465-fold lower than for the A2A receptor), and >10,000 nM for the adenosine A2B and A3 receptors (>690-fold lower than for the A2A receptor).[3][4]

MSX-2 has poor water solubility, which has limited the use of MSX-2 itself.[1][5] Water-soluble ester prodrugs of MSX-2, including MSX-3 (a phosphate ester prodrug) and MSX-4 (an amino acid ester prodrug), have been developed and used in place of MSX-2.[1][5] MSX-3 is best-suited for use by intravenous administration, whereas MSX-4 can be administered by oral administration.[5][6]

MSX-3 and MSX-4 reverse motivational deficits in animals and hence have the capacity to produce pro-motivational effects.[7][8][9]

MSX-2 and MSX-3 were first described in the scientific literature by 1998.[10][11] Subsequently, MSX-4 was developed and described by 2008.[5][6]

See also

References

  1. ^ a b c d de Lera Ruiz M, Lim YH, Zheng J (May 2014). "Adenosine A2A receptor as a drug discovery target". Journal of Medicinal Chemistry. 57 (9): 3623–3650. doi:10.1021/jm4011669. PMID 24164628.
  2. ^ Yuzlenko O, Kieć-Kononowicz K (2006). "Potent adenosine A1 and A2A receptors antagonists: recent developments". Current Medicinal Chemistry. 13 (30): 3609–3625. doi:10.2174/092986706779026093. PMID 17168726.
  3. ^ Khayat MT, Hanif A, Geldenhuys WJ, Nayeem MA (2019). "Adenosine Receptors and Drug Discovery in the Cardiovascular System". In Choudhary MI (ed.). Frontiers in Cardiovascular Drug Discovery: Volume 4. Amazon Digital Services LLC - Kdp. pp. 16–64. ISBN 978-1-68108-400-8. Retrieved 23 September 2024.
  4. ^ Müller CE, Jacobson KA (May 2011). "Recent developments in adenosine receptor ligands and their potential as novel drugs". Biochim Biophys Acta. 1808 (5): 1290–1308. doi:10.1016/j.bbamem.2010.12.017. PMC 3437328. PMID 21185259.
  5. ^ a b c d Müller CE (November 2009). "Prodrug approaches for enhancing the bioavailability of drugs with low solubility". Chemistry & Biodiversity. 6 (11): 2071–2083. doi:10.1002/cbdv.200900114. PMID 19937841.
  6. ^ a b Vollmann K, Qurishi R, Hockemeyer J, Müller CE (February 2008). "Synthesis and properties of a new water-soluble prodrug of the adenosine A 2A receptor antagonist MSX-2". Molecules. 13 (2): 348–359. doi:10.3390/molecules13020348. PMC 6244838. PMID 18305423.
  7. ^ 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". Pharmacological Reviews. 70 (4): 747–762. doi:10.1124/pr.117.015107. PMC 6169368. PMID 30209181.
  8. ^ López-Cruz L, Salamone JD, Correa M (2018). "Caffeine and Selective Adenosine Receptor Antagonists as New Therapeutic Tools for the Motivational Symptoms of Depression". Frontiers in Pharmacology. 9: 526. doi:10.3389/fphar.2018.00526. PMC 5992708. PMID 29910727.
  9. ^ Salamone JD, Correa M, Farrar AM, Nunes EJ, Collins LE (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. hdl:10234/35900. ISSN 1479-6708.
  10. ^ Müller CE, Sauer R, Maurinsh Y, Huertas R, Fülle F, Klotz KN, Nagel J, Hauber W (1998). "A2A-selective adenosine receptor antagonists: Development of water-soluble prodrugs and a new tritiated radioligand". Drug Development Research. 45 (3–4): 190–197. doi:10.1002/(SICI)1098-2299(199811/12)45:3/4<190::AID-DDR16>3.0.CO;2-A. ISSN 0272-4391.
  11. ^ 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.


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