MSX-3
Selective adenosine A2A receptor antagonist used in scientific research
From Wikipedia, the free encyclopedia
MSX-3 is a selective adenosine A2A receptor antagonist used in scientific research.[1][2] Similarly to MSX-4, it is a water-soluble ester prodrug of MSX-2.[2][3][4]
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| Drug class | Adenosine A2A receptor antagonist |
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| Formula | C21H23N4O7P |
| Molar mass | 474.410 g·mol−1 |
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Medicinal chemistry
MSX-3, MSX-4, and MSX-2 are xanthines and are derivatives of the non-selective adenosine receptor antagonist caffeine.[5][6] MSX-2 has been extensively studied due to its high affinity and selectivity for the adenosine A2A receptor, but use of MSX-2 itself has been limited by its poor water solubility.[5][2]
Whereas MSX-3 is a phosphate ester prodrug of MSX-2 that is suited best for intravenous administration and not for oral administration, MSX-4 is an amino acid ester (L-valine) prodrug of MSX-2 that can be orally administered.[2][7]
Pharmacology
MSX-2 has 500-fold higher affinity for the adenosine A2A receptor over the adenosine A1 receptor, 580-fold higher affinity for the adenosine A2A receptor over the adenosine A2B receptor, and is inactive at the adenosine A3 receptor.[5][6][8]
MSX-3 itself also showed some affinity for the adenosine receptors, but this may have just been due to degradation by phosphatases in the in vitro system.[6]
Animal studies
MSX-3 shows pro-motivational effects in animals.[1][9] 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][9][10][11][12][13]
Conversely, it only mildly attenuates the motivational deficits induced by the dopamine D1 receptor antagonist ecopipam (SCH-39166).[10][14]
History
MSX-3 was first described in the scientific literature by 1998.[3][4] A similar agent, MSX-4, was subsequently described by 2008.[2][7]