dizocilpine-maleate and 3-7-dimethyl-1-propargylxanthine

Interactions between adenosine receptor ligands and dizocilpine (uncompetitive NMDA receptor antagonist) was studied in antinociceptive, writhing test in mice. Minimal effective, antinociceptive doses of adenosine receptor agonists were: 0.1 mg/kg (NECA--A1/A2 agonist). Generally, these agonists did not potentiate the subthreshold dose of dizocilpine (0.05 mg/kg). Of all adenosine receptor antagonists used, only caffeine (A2 and A2 antagonists) reversed dizocilpine-induced (0.1 mg/kg) antinociception dose-dependently. These findings indicate that dizocilpin-induced antinociception in the writhing test is only partly influenced by adenosine receptor ligands.

Topics: Acetic Acid; Animals; Behavior, Animal; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Male; Mice; Nociceptors; Pain; Purinergic P1 Receptor Agonists; Receptors, Purinergic P1; Theobromine; Xanthines

Glutamate has been shown to play an important role in delayed neuronal cell death occurring due to ischemia. Attenuation of synaptically released glutamate can be accomplished by modulators such as adenosine and baclofen. This study focused on the ability of adenosine to attenuate the excitotoxicity secondary to glutamate receptor activation in vitro after exposure to potassium cyanide (KCN) in hippocampal neuronal cell cultures. For this study, hippocampal cell cultures were obtained from 1-day-old rats and trypan blue staining was used for assessment of cell viability. It was found that the N-methyl-D-aspartate-specific antagonist MK801 (10 microM) attenuated neuronal cell death resulting from exposure to 1 mM KCN for 60 minutes. Adenosine (10 to 1000 microM) decreased neuronal cell death secondary to the same concentration of KCN in a dose-dependent manner. This same neuroprotective effect is mimicked by the adenosine A1-specific receptor agonist N6-cyclopentyladenosine (10 microM). The A1-specific receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (10 to 1000 nM) blocked the neuroprotective effect of adenosine in a dose-dependent manner. Therefore, neuronal cell death produced by KCN in the experimental model described was mediated at least in part by glutamate. This neuronal cell death was attenuated by adenosine via the A1-specific mechanism.

Topics: Adenosine; Animals; Cell Death; Cells, Cultured; Dizocilpine Maleate; Hippocampus; Neurons; Osmolar Concentration; Potassium Cyanide; Purinergic Antagonists; Theobromine; Theophylline