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Adenosine receptor subtype-selective antagonists in inflammation and hyperalgesia

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Abstract

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 A3 receptor antagonism, also after the carrageenan injection. The selective A2B 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. A1 and A2B antagonists diminished pain-related behaviors in the first phase of the formalin test, while the second, inflammatory phase was attenuated by A2B and A3 antagonists. The A2B 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 A2A antagonist MSX-3 at a dose of 10 mg/kg. In contrast to the A1 antagonist, the selective antagonists of A2A, A2B, and A3 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 A2A antagonists may be useful for the treatment of inflammatory hyperalgesia, while A2B antagonists have potential as analgesic drugs for the treatment of inflammatory pain.

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Acknowledgements

We thank the members of the laboratory for suggestions on the experiments and the manuscript. This work was supported by grants from the Deutsche Forschungsgemeinschaft (FOR425), the State of North-Rhine-Westfalia (Innovationsprogramm Forschung), and the BONFOR Program.

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  1. Osama M. Abo-Salem

    Present address: Department of Pharmacology and Toxicology, Al-Azhar University, Cairo, Egypt

  2. Alaa M. Hayallah

    Present address: Faculty of Pharmacy, Assiut University, Assiut, Egypt

Authors and Affiliations

  1. Institute of Molecular Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53127,, Bonn, Germany

    Andras Bilkei-Gorzo, Osama M. Abo-Salem, Kerstin Michel & Andreas Zimmer

  2. Pharmaceutical Institute, University of Bonn, Bonn, Germany

    Alaa M. Hayallah & Christa E. Müller

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  1. Andras Bilkei-Gorzo
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Correspondence to Andras Bilkei-Gorzo.

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Bilkei-Gorzo, A., Abo-Salem, O.M., Hayallah, A.M. et al. Adenosine receptor subtype-selective antagonists in inflammation and hyperalgesia. Naunyn-Schmied Arch Pharmacol 377, 65–76 (2008). https://doi.org/10.1007/s00210-007-0252-9

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