A tertiary amine tricyclic antidepressant that is thought
to exert its therapeutic effect by inhibiting the reuptake of serotonin
and norepinephrine centrally. A major metabolite is N-desmethylimipramine
(desipramine), also used as an antidepressant
drug. Desipramine differs from imipramine in being a better
blocker of norepinephrine, rather than serotonin, uptake. Side
effects, including sedation and drowsiness, dry mouth, urinary
retention, constipation, and orthostatic hypotension, are probably
due to the anticholinergic, anti-α-adrenergic, and antihistaminergic
receptor-blocking properties. Imipramine should not be used
in conjunction with a monoamine oxidase inhibitor or other
treatment that increases catecholamine concentrations (e.g.,
drugs containing sympathomimetic amines). Imipramine should
be avoided in patients with cardiovascular disease or seizure disorder,
or in those who may abuse alcohol, as imipramine lowers
seizure threshold, can produce cardiovascular toxicity and may
potentiate the effects of alcohol. Imipramine intoxication can
include CNS abnormalities (e.g., drowsiness, stupor, coma, and
extrapyramidal symptoms), cardiac arrhythmia, and respiratory
depression. Children appear to be particularly vulnerable to the
cardiotoxic and seizure-inducing effects of high doses of imipramine.
The oral LD50 in female rats is 305 mg/kg.
Imipramine is used in depression of various etiology accompanied by motor
clumsiness and enuresis in children and Parkinson’s disease.
Mechanism of action
Besides being used in the clinical treatment of depression, imipramine also has been used for the treatment
of functional enuresis in children who are at least 6 years of age (25 mg daily administered 1 hour before
bedtime, not to exceed 2.5 mg/kg daily).
Clinical Use
Imipramine is a 10,11-dihydrodibenzazepine tertiary amine TCA that is marketed as hydrochloride
and pamoate salts, both of which are administered orally. Although the hydrochloride salt may be
administered in divided daily doses, imipramine's long duration of action suggests that the entire oral daily
dose may be administered at one time.On the other hand, imipramine pamoate usually is administered as a
single daily oral dose.
