Imipramine is a well-established
tricyclic antidepressant which was first approved for the treatment of depression in the late fifties.
Antidepressant effect of
imipramine is attributed to inhibition of
serotonin (5HT) and
noradrenaline (NA) reuptake in brain. These monoamines have been implicated in a variety of
neurological disorders including
tremor. In the present investigation attempt was made to study the effect of
imipramine on
harmaline-induced
tremor in rats. Male Sprague Dawley rats weighing 115+/-2.5 g were given
harmaline (10 mg/kg, i.p.) alone or along with
imipramine (30 min before
harmaline) in doses of 60 and 90 mg/kg respectively. The latency of onset, intensity and duration of
tremor and EMG were recorded. To substantiate the role of 5HT in aetiopathology of
tremor the above experiment was repeated in the rats pretreated with
P-chlorophenylalanine (PCPA), a potent 5HT depleter. The levels of 5HT and
5-hydroxyindole acetic acid (5HIAA) in the brain stem were measured using high performance liquid chromatography.
Imipramine dose-dependently exacerbated the duration, intensity and amplitude of EMG following
harmaline-induced
tremor.
Imipramine treatment further decreased
harmaline-induced 5HT turnover in the brain stem. However, this was statistically insignificant. Depletion of 5HT produced a significant reduction in the intensity and duration of
harmaline-induced
tremor. In conclusion, this study suggests that
imipramine exacerbates
harmaline-induced
tremor. Clinical use of
imipramine for the treatment of depression in patients who also suffer from
tremors may require a close monitoring.