Anti-inflammatory, antioxidant, and antiparkinsonian effects of adenosine A2Areceptor antagonists.
The purpose of the study was to examine derivatives of annelated xanthines (imidazo-, pyrimido-, and diazepino-purinediones) for potential anti-inflammatory effects in carrageenan-induced paw edema in mice. Additionally, their antioxidant activity using the FRAP (ferric-reducing ability of plasma) assay and lipid peroxidation in rat brain homogenate were analyzed. All the studied derivatives showed affinity for adenosine A2Areceptor. The preliminary assays found that five (KD-114, KD-57, KD-129, KD-50, and KD-358) pyrimidopurinedione derivatives, administered intraperitoneally (i.p.) at a dose of 100mg/kg, had stronger anti-inflammatory effects. At a concentration of 10-5M, three of the derivatives KD-57, KD-114, and KD-129 most influenced the total antioxidant ability. The most efficient anti-inflammatory compound, KD-114, also showed the strongest binding to A2Areceptors and when administered at a dose of 5mg/kg (i.p.), effectively reversed haloperidol-induced catalepsy and significantly increased the striatal extracellular dopamine level in the rat striatum. This effect was weaker than the one produced by CSC (1mg/kg i.p.), and only slightly weaker than that produced by ZM 241385 (3mg/kg i.p.) used as reference drugs. From the results of the present studies, it may be concluded that anti-inflammatory and antiparkinsonian effects of the examined compounds correlate with their influence on adenosine A2Areceptors, the most probable antagonism to these subtype receptors.
Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, 9 Medyczna Street, PL 30-688 Krakow, Poland. Electronic address: gogol67@interia.pl.
Małgorzata
M
Zygmunt
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland; Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Krystyna
K
Gołembiowska
Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, 9 Medyczna Street, PL 30-688 Krakow, Poland.
Anna
A
Drabczyńska
Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, 9 Medyczna Street, PL 30-688 Krakow, Poland.
Katarzyna
K
Kieć-Kononowicz
Department of Pharmacological Screening, Chair of Pharmacodynamics, Jagiellonian University, Medical College, 9 Medyczna Street, PL 30-688 Krakow, Poland.
Jacek
J
Sapa
Annelated xanthines; Anti-inflammatory activity; Catalepsy