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

• Published in: Drug and chemical toxicology (New York, N.Y. 1978) N.Y. 1978), 2010-07, Vol.33 (3), p.233-237
• Main Authors: Kalkan, Sule, Hocaoglu, Nil, Arici, Aylin (Akgun), Oransay, Kubilay, Ergor, Gul, Tuncok, Yesim
• Format: Article
• Language: English
• Subjects: Adenosine A1 Receptor Antagonists; Adenosine A2 Receptor Antagonists; adenosine antagonist; Amitriptyline; Amitriptyline - poisoning; Animals; Antidepressive Agents, Tricyclic - poisoning; Dose-Response Relationship, Drug; Kaplan-Meier Estimate; Lethal Dose 50; Male; Mice; Mice, Inbred BALB C; Random Allocation; Receptor, Adenosine A1 - metabolism; Receptor, Adenosine A2A - metabolism; survival rate; Xanthines - pharmacology
• ISSN: 0148-0545; 1525-6014
• DOI: 10.3109/01480540903130690

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.