Adenosine receptor agonists or antagonists alter antinociception, but did not show an interaction with imipramine-induced antinociception in the formalin test in mice

Abstract

In this study, the antinociceptive effect of imipramine and adenosine agents, and interactions between imipramine with adenosine drugs in mice in the formalin test, have been investigated. Intraperitoneal administration of different doses of imipramine (10, 20, 30 and 40 mg/kg) induced a dose dependent antinociception in mice, in both the first and second phases of the formalin test. The adenosine A1 receptor agonists, R-(N6-phenylisopropyl)-adenosine (0.015, 0.03 and 0.1 mg/kg) and 5′-N-ethylcarboxamide adenosine (0.001, 0.005, 0.01 mg/kg), but not 2-chloroadenosine (0.1 and 0.5 mg/kg), and the adenosine receptor antagonist, 8-phenyltheophylline (0.1, 0.5 and 1 mg/kg), but not 1,3-dipropyl-7-methyl-xanthine (0.5 and 5 mg/kg), also produced an antinociceptive response. Lower dose of the adenosine receptor antagonist theophylline induced antinociception, while a higher dose of the drug caused hyperalgesia. Theophylline reduced the response induced by imipramine. It is concluded that adenosine systems are not involved in imipramine responses in the formalin test.