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Effects of Adenosine Receptor Antagonists on Survival in Amitriptyline-poisoned Mice

Objective: We investigated the effects of adenosine receptor antagonists on survival rates in a mouse model of amitriptyline poisoning. Materials and Methods: In the preliminary study, amitriptyline was given at doses of 75, 100, and 125 mg/ kg to mice intraperitoneally (i.p.; n = 20 for each dose) to determine the lethal dose at 50% (LD50). Different doses (1, 3, and 5 mg/kg) of DPCPX (selective adenosine A1 antagonists, n = 10 for each dose, total n = 30) or CSC (selective adenosine A2a antagonists, n = 10 for each dose, total n = 30) were given i.p. to find the nonlethal dose. After the administration of the LD50 dose of amitriptyline (125 mg/kg), mice were treated with DPCPX (3 mg/kg), CSC (3 mg/kg), saline, or DMSO (dimethyl sulfoxide) (n = 25 for each group). Mice were observed during a 24-hour period. Results: Kaplan-Meier estimates of the 24-hour survival rate was 52% (13/25) for saline and 68% (17/25), 52% (13/25), and 40% (10/25) for the DPCPX, CSC, and DMSO groups, respectively. There was no statistically significant difference in survival rates among the groups (P > 0.05). Conclusions: Adenosine antagonists failed to increase the survival rates of amitriptyline-poisoned mice. Further studies are needed with repeated doses of adenosine antagonists.