SCH-58261
SCH-58261 Structure.svg
Clinical data
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Identifiers
  • 5-Amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18H15N7O
Molar mass345.366 g·mol−1
3D model (JSmol)
  • c1ccccc1CCN1N=CC2=C1N=C(N)N3C2=NC(C4=CC=CO4)=N3
  • InChI=1S/C18H15N7O/c19-18-22-16-13(11-20-24(16)9-8-12-5-2-1-3-6-12)17-21-15(23-25(17)18)14-7-4-10-26-14/h1-7,10-11H,8-9H2,(H2,19,22) checkY
  • Key:UTLPKQYUXOEJIL-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

SCH-58261 is a drug which acts as a potent and selective antagonist for the adenosine receptor A2A, with more than 50x selectivity for A2A over other adenosine receptors.[1] It has been used to investigate the mechanism of action of caffeine, which is a mixed A1 / A2A antagonist, and has shown that the A2A receptor is primarily responsible for the stimulant and ergogenic effects of caffeine,[2] but blockade of both A1 and A2A receptors is required to accurately replicate caffeine's effects in animals.[3][4][5][6] SCH-58261 has also shown antidepressant,[7] nootropic and neuroprotective effects in a variety of animal models,[8][9][10][11][12][13] and has been investigated as a possible treatment for Parkinson's disease.[14][15]

See also

References

  1. ^ Zocchi C, Ongini E, Conti A, Monopoli A, Negretti A, Baraldi PG, Dionisotti S (February 1996). "The non-xanthine heterocyclic compound SCH 58261 is a new potent and selective A2a adenosine receptor antagonist". The Journal of Pharmacology and Experimental Therapeutics. 276 (2): 398–404. PMID 8632302.
  2. ^ Aguiar AS, Speck AE, Canas PM, Cunha RA (August 2020). "Neuronal adenosine A2A receptors signal ergogenic effects of caffeine". Scientific Reports. 10 (1): 13414. Bibcode:2020NatSR..1013414A. doi:10.1038/s41598-020-69660-1. PMC 7415152. PMID 32770138.
  3. ^ Svenningsson P, Nomikos GG, Ongini E, Fredholm BB (August 1997). "Antagonism of adenosine A2A receptors underlies the behavioural activating effect of caffeine and is associated with reduced expression of messenger RNA for NGFI-A and NGFI-B in caudate-putamen and nucleus accumbens". Neuroscience. 79 (3): 753–64. doi:10.1016/S0306-4522(97)00046-8. PMID 9219939. S2CID 21130714.
  4. ^ Popoli P, Reggio R, Pèzzola A, Fuxe K, Ferré S (July 1998). "Adenosine A1 and A2A receptor antagonists stimulate motor activity: evidence for an increased effectiveness in aged rats". Neuroscience Letters. 251 (3): 201–4. doi:10.1016/S0304-3940(98)00533-3. PMID 9726378. S2CID 26570997.
  5. ^ El Yacoubi M, Ledent C, Ménard JF, Parmentier M, Costentin J, Vaugeois JM (April 2000). "The stimulant effects of caffeine on locomotor behaviour in mice are mediated through its blockade of adenosine A(2A) receptors". British Journal of Pharmacology. 129 (7): 1465–73. doi:10.1038/sj.bjp.0703170. PMC 1571962. PMID 10742303.
  6. ^ Kuzmin A, Johansson B, Gimenez L, Ogren SO, Fredholm BB (February 2006). "Combination of adenosine A1 and A2A receptor blocking agents induces caffeine-like locomotor stimulation in mice". European Neuropsychopharmacology. 16 (2): 129–36. doi:10.1016/j.euroneuro.2005.07.001. PMID 16054807. S2CID 39153884.
  7. ^ El Yacoubi M, Costentin J, Vaugeois JM (December 2003). "Adenosine A2A receptors and depression". Neurology. 61 (11 Suppl 6): S82-7. doi:10.1212/01.WNL.0000095220.87550.F6. PMID 14663017. S2CID 36219448.
  8. ^ Monopoli A, Lozza G, Forlani A, Mattavelli A, Ongini E (December 1998). "Blockade of adenosine A2A receptors by SCH 58261 results in neuroprotective effects in cerebral ischaemia in rats". NeuroReport. 9 (17): 3955–9. doi:10.1097/00001756-199812010-00034. PMID 9875735. S2CID 34804980.
  9. ^ Popoli P, Pintor A, Domenici MR, Frank C, Tebano MT, Pèzzola A, et al. (March 2002). "Blockade of striatal adenosine A2A receptor reduces, through a presynaptic mechanism, quinolinic acid-induced excitotoxicity: possible relevance to neuroprotective interventions in neurodegenerative diseases of the striatum". The Journal of Neuroscience. 22 (5): 1967–75. doi:10.1523/jneurosci.22-05-01967.2002. PMC 6758877. PMID 11880527.
  10. ^ Melani A, Gianfriddo M, Vannucchi MG, Cipriani S, Baraldi PG, Giovannini MG, Pedata F (February 2006). "The selective A2A receptor antagonist SCH 58261 protects from neurological deficit, brain damage and activation of p38 MAPK in rat focal cerebral ischemia". Brain Research. 1073–1074: 470–80. doi:10.1016/j.brainres.2005.12.010. PMID 16443200. S2CID 26319608.
  11. ^ Minghetti L, Greco A, Potenza RL, Pezzola A, Blum D, Bantubungi K, Popoli P (May 2007). "Effects of the adenosine A2A receptor antagonist SCH 58621 on cyclooxygenase-2 expression, glial activation, and brain-derived neurotrophic factor availability in a rat model of striatal neurodegeneration". Journal of Neuropathology and Experimental Neurology. 66 (5): 363–71. doi:10.1097/nen.0b013e3180517477. PMID 17483693.
  12. ^ Canas PM, Porciúncula LO, Cunha GM, Silva CG, Machado NJ, Oliveira JM, et al. (November 2009). "Adenosine A2A receptor blockade prevents synaptotoxicity and memory dysfunction caused by beta-amyloid peptides via p38 mitogen-activated protein kinase pathway". The Journal of Neuroscience. 29 (47): 14741–51. doi:10.1523/JNEUROSCI.3728-09.2009. PMC 6665997. PMID 19940169.
  13. ^ Mouro FM, Köfalvi A, André LA, Baqi Y, Müller CE, Ribeiro JA, Sebastião AM (September 2019). "Memory deficits induced by chronic cannabinoid exposure are prevented by adenosine A2AR receptor antagonism". Neuropharmacology. 155: 10–21. doi:10.1016/j.neuropharm.2019.05.003. PMID 31103616.
  14. ^ Chen JF, Xu K, Petzer JP, Staal R, Xu YH, Beilstein M, et al. (May 2001). "Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson's disease". The Journal of Neuroscience. 21 (10): RC143. doi:10.1523/JNEUROSCI.21-10-j0001.2001. PMC 6762498. PMID 11319241.
  15. ^ Simola N, Fenu S, Baraldi PG, Tabrizi MA, Morelli M (October 2006). "Dopamine and adenosine receptor interaction as basis for the treatment of Parkinson's disease". Journal of the Neurological Sciences. 248 (1–2): 48–52. doi:10.1016/j.jns.2006.05.038. PMID 16780890. S2CID 26841529.