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Neurosci Lett. 2014 Jan 13;558:203-7. doi: 10.1016/j.neulet.2013.10.035. Epub 2013 Oct 22.

8-(Furan-2-yl)-3-phenethylthiazolo[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione as novel, selective and potent adenosine A(2A) receptor antagonist.

Author information

  • 1Neuropharmaceutical Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi 110007, India.
  • 2Neuropharmaceutical Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, Mall Road, Delhi 110007, India. Electronic address: pmlsci@yahoo.com.

Abstract

Antagonism of the human A2A receptor has been implicated to alleviate the symptoms associated with Parkinson's disease. The present finding reveals the potential of PTTP (8-(furan-2-yl)-3-phenethylthiazolo[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione) as novel and potent A2AR antagonist. In radioligand binding assay, PTTP showed significantly high binding affinity (Ki 6.3 nM) and selectivity with A2AR (A1R/A2AR=4603) which was comparable to the results of docking analysis (Ki=1.6 nM, ΔG=-14.52 Kcal/mol). PTTP antagonized (0.46 pmol/ml) the effect of NECA-induced increase in cAMP concentration (0.65 pmol/ml) better than SCH58261 (0.55 pmol/ml) in HEK293T cells. Haloperidol and NECA-induced mice pre-treated with PTTP at 10mg/kg showed attenuation in catalepsy and akinesia without significant neurotoxicity in rotarod test at 20mg/kg. Essentially, novel compound demonstrated remarkable potential as A2AR antagonist in the therapy of PD.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS:

Adenosine A(2A) receptors (A(2A)R); Catalepsy; Motor activity; Mouse models of Parkinson; PTTP; cAMP

PMID:
24161891
[PubMed - indexed for MEDLINE]
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