Synthesis and Analgesic Activity of Annelated Xanthine Derivatives in Experimental Models in Rodents

Arch Pharm (Weinheim). 2015 Oct;348(10):704-14. doi: 10.1002/ardp.201500169. Epub 2015 Aug 6.

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.

Keywords: Adenosine receptors; Analgesic activity; Pyrimido[2,1-f]purinediones; Xanthines.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / chemical synthesis*
  • Analgesics / metabolism
  • Analgesics / pharmacology*
  • Analgesics / toxicity
  • Animals
  • Aspirin / pharmacology
  • Behavior, Animal / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Design
  • Drug Interactions
  • HEK293 Cells
  • Humans
  • Inhibitory Concentration 50
  • Male
  • Mice
  • Molecular Structure
  • Motor Activity / drug effects
  • Pain / physiopathology
  • Pain / prevention & control*
  • Pain Threshold / drug effects
  • Rats
  • Reaction Time / drug effects
  • Receptors, Purinergic P1 / drug effects
  • Receptors, Purinergic P1 / metabolism
  • Structure-Activity Relationship
  • Xanthines / chemical synthesis*
  • Xanthines / metabolism
  • Xanthines / pharmacology*
  • Xanthines / toxicity

Substances

  • Analgesics
  • Receptors, Purinergic P1
  • Xanthines
  • Aspirin