In this study, we examined the effects of systemic and local administration of the subtype-selective
adenosine receptor antagonists PSB-36,
PSB-1115, MSX-3, and PSB-10 on
inflammation and inflammatory
hyperalgesia. Pharmacological blockade of
adenosine receptor subtypes after systemic application of antagonists generally led to a decreased
edema formation after
formalin injection and, with the exception of A(3) receptor antagonism, also after the
carrageenan injection. The selective A(2B) receptor antagonist
PSB-1115 showed a biphasic, dose-dependent effect in the
carrageenan test, increasing
edema formation at lower doses and reducing it at a high dose. A(1) and A(2B) antagonists diminished
pain-related behaviors in the first phase of the
formalin test, while the second, inflammatory phase was attenuated by A(2B) and A(3) antagonists. The A(2B) antagonist was particularly potent in reducing inflammatory
pain dose-dependently reaching the maximum effect at a low dose of 3 mg/kg. Inflammatory
hyperalgesia was totally eliminated by the A(2A) antagonist MSX-3 at a dose of 10 mg/kg. In contrast to the A(1) antagonist, the selective antagonists of A(2A), A(2B), and A(3) receptors were also active upon local administration. Our results demonstrate that the blockade of
adenosine receptor subtypes can decrease the magnitude of inflammatory responses. Selective A(2A) antagonists may be useful for the treatment of inflammatory
hyperalgesia, while A(2B) antagonists have potential as
analgesic drugs for the treatment of inflammatory
pain.