Behavioural and neurochemical characterization of the adenosine A2A receptor antagonist ST1535.
ST1535 (2-butyl-9-methyl-8-(2H-1,2,3-triazol 2-yl)-9 H-purin-6-ylamine) is a novel compound showing a preferential adenosine A(2A) receptor antagonist profile. To explore the potential neuroprotective profile of this compound, we evaluated whether ST1535 prevented quinolinic acid (QA)-induced glutamate outflow in the rat striatum (a reliable index of neuroprotective activity in vivo). Microdialysis experiments were performed in naive Wistar rats. In these experiments, a behaviourally active and inactive doses of ST1535 were used. Both doses significantly prevented QA-induced glutamate outflow in the striatum. These results show that ST1535 protects towards striatal excitotoxicity, even though its reduced A(2A)/A(1) selectivity might limit its actual neuroprotective potential.
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome (Italy).
Mariangela
M
Galluzzo
Anita
A
Pintor
Antonella
A
Pèzzola
Rosa
R
Grieco
Franco
F
Borsini
Patrizia
P
Popoli
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017378:Quinolinic Acid; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
C506291:2-n-butyl-9-methyl-8-(1,2,3)triazol-2-yl-9H-purin-6-ylamine; D058917:Adenosine A2 Receptor Antagonists; D018696:Neuroprotective Agents; D014230:Triazoles; D018698:Glutamic Acid; D017378:Quinolinic Acid; D000225:Adenine