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Drug Chem Toxicol ; 33(3): 233-7, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20429795

ABSTRACT

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 A(1) 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.


Subject(s)
Adenosine A1 Receptor Antagonists , Adenosine A2 Receptor Antagonists , Amitriptyline/poisoning , Antidepressive Agents, Tricyclic/poisoning , Xanthines/pharmacology , Animals , 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
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