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.


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.
Kalkan
Sule
S
Department of Pharmacology, Dokuz Eylul University School of Medicine, Izmir, Turkey. sule.kalkan@deu.edu.tr
Hocaoglu
Nil
N
Arici
Aylin Akgun
AA
Oransay
Kubilay
K
Ergor
Gul
G
Tuncok
Yesim
Y
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000639:Amitriptyline / Q000506:poisoning*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000506:poisoning*; D004305:Dose-Response Relationship, Drug; D053208:Kaplan-Meier Estimate; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011897:Random Allocation; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology*
C515416:8-(3-Chlorostyryl)-1,3,7-trimethylxanthine; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000929:Antidepressive Agents, Tricyclic; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D014970:Xanthines; D000639:Amitriptyline; C051360:1,3-dipropyl-8-cyclopentylxanthine