title: Synthesis and Analgesic Activity of Annelated Xanthine Derivatives in Experimental Models in Rodents.
abstract: A series of annelated derivatives of xanthine were synthesized and assayed as potential analgesic agents. All synthesized xanthine derivatives were tested in the writhing test and hot-plate test. The pharmacological assays demonstrated that all the compounds prepared, without exception, displayed a significant activity in the mouse writhing assay. The analgesic action of the most active compounds, expressed as ED50 was found to be 1.4-4.3 times more potent than that of acetylsalicylic acid used as the reference compound. However, only some of the compounds demonstrated analgesic activity in the hot-plate test. The analgesic effect of some compounds is probably related to their agonistic, antagonistic, or partial agonistic activity at the adenosine receptors.
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Drabczyńska
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Karcz
authors.affiliation: PharmaCenter Bonn, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Müller
authors.affiliation: PharmaCenter Bonn, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
authors.forename: Meryem
authors.initials: M
authors.lastname: Köse
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Gniewomir
authors.initials: G
authors.lastname: Latacz
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Schabikowski
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bednarski
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kieć-Kononowicz
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004347:Drug Interactions; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000700:Analgesics; D018047:Receptors, Purinergic P1; D014970:Xanthines; D001241:Aspirin
keywords: Adenosine receptors; Analgesic activity; Pyrimido[2,1-f]purinediones; Xanthines