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

摘要

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% (LD_(50)). 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 A_(2a) antagonists, n = 10 for each dose, total n = 30) were given i.p. to find the nonlethal dose. After the administration of the LD_(50) 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.