Interestingly, excitotoxicity prevention by the A2A receptor antagonist appears to be time dependent, and while A2A receptor antagonist SCH58261 completely blocked the induced glutamate release in rat striatum,117 its effect was reversed 2 weeks after the treatment.105 Remarkably, this spontaneous glutamate release in response to SCH58261 treatment was different in young rats compared to the aged ones.104 Additionally, recent study suggested that, although A2A receptor antagonists initially protected against transient ischemic injury, this protective effect disappeared 7 days after ischemia and despite continued treatment with the antagonist.118
