Chemistry:MSX-2
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
- 3-Chlorostyrylcaffeine
- Istradefylline
- Preladenant
References
- ↑ 1.0 1.1 1.2 1.3 "Adenosine A2A receptor as a drug discovery target". Journal of Medicinal Chemistry 57 (9): 3623–3650. May 2014. doi:10.1021/jm4011669. PMID 24164628.
- ↑ "Potent adenosine A1 and A2A receptors antagonists: recent developments". Current Medicinal Chemistry 13 (30): 3609–3625. 2006. doi:10.2174/092986706779026093. PMID 17168726.
- ↑ "Adenosine Receptors and Drug Discovery in the Cardiovascular System". Frontiers in Cardiovascular Drug Discovery: Volume 4. Amazon Digital Services LLC - Kdp. 2019. pp. 16–64. ISBN 978-1-68108-400-8. https://books.google.com/books?id=R6SXDwAAQBAJ&pg=PA16. Retrieved 23 September 2024.
- ↑ "Recent developments in adenosine receptor ligands and their potential as novel drugs". Biochim Biophys Acta 1808 (5): 1290–1308. May 2011. doi:10.1016/j.bbamem.2010.12.017. PMID 21185259.
- ↑ 5.0 5.1 5.2 5.3 "Prodrug approaches for enhancing the bioavailability of drugs with low solubility". Chemistry & Biodiversity 6 (11): 2071–2083. November 2009. doi:10.1002/cbdv.200900114. PMID 19937841.
- ↑ 6.0 6.1 "Synthesis and properties of a new water-soluble prodrug of the adenosine A 2A receptor antagonist MSX-2". Molecules 13 (2): 348–359. February 2008. doi:10.3390/molecules13020348. PMID 18305423.
- ↑ "The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine, and Insights into the Neurochemistry of Motivation". Pharmacological Reviews 70 (4): 747–762. October 2018. doi:10.1124/pr.117.015107. PMID 30209181.
- ↑ "Caffeine and Selective Adenosine Receptor Antagonists as New Therapeutic Tools for the Motivational Symptoms of Depression". Frontiers in Pharmacology 9: 526. 2018. doi:10.3389/fphar.2018.00526. PMID 29910727.
- ↑ "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. 5 May 2010. doi:10.2217/fnl.10.19. ISSN 1479-6708.
- ↑ "A2A-selective adenosine receptor antagonists: Development of water-soluble prodrugs and a new tritiated radioligand". Drug Development Research 45 (3–4): 190–197. 1998. doi:10.1002/(SICI)1098-2299(199811/12)45:3/4<190::AID-DDR16>3.0.CO;2-A. ISSN 0272-4391.
- ↑ "Motor effects induced by a blockade of adenosine A2A receptors in the caudate-putamen". NeuroReport 9 (8): 1803–1806. June 1998. doi:10.1097/00001756-199806010-00024. PMID 9665604.
 |  |
