Acute toxicity profile of maprotiline in the rat

The aim of the present study was to examine the toxic effects of single oral administrations of the antidepressant maprotiline at 150 mg/kg or 300 mg/kg using female Sprague-Dawley rats. Body-weight gain was significantly reduced in the group receiving 300 mg/kg on days 1-5 of the study (P<0.01). A significant reduction in food and water intake was observed on days 1 and 2 of the study (P<0.01) in the 300 mg/kg group and on day 1 in the 150 mg/kg group (P<0.05). There was a significant decrease in nocturnal home cage activity over the first five days of the study in the 300 mg/kg group (P<0.01). A significant hypothermic response was observed in both 150 and 300 mg/kg groups at 1, 2 and 4 hr after dosing (P<0.01), that had returned to control values within 8 hr following administration. This study demonstrates that a multi-parameter approach is appropriate for the investigation of high doses of antidepressants in rodents.