Products
Imipramine was commercially available in the form of dragées (Tofranil). It was developed at Geigy in Basel. Its antidepressant properties were discovered in the 1950s by Roland Kuhn at the psychiatric clinic in Münsterlingen (Thurgau). It was approved in many countries in 1958 as the first active ingredient in the tricyclic antidepressant group. In 2017, it was discontinued by Novartis.
Structure and properties
Imipramine (C19H24N2, Mr = 280.4 g/mol) is present as imipramine hydrochloride, a white to pale yellow crystalline powder that is readily soluble in water. It is a dibenzazepine and was developed starting from chlorpromazine. The active -desmethyl metabolite desipramine is mainly responsible for reuptake inhibition of norepinephrine.
Effects
Imipramine (ATC N06AA02) has antidepressant (mood elevating), sedative, antinociceptive, and anticholinergic properties. The effects are primarily attributed to inhibition of the reuptake of norepinephrine and, to a lesser extent, serotonin into presynaptic neurons. Imipramine is additionally an antagonist at alpha-adrenoceptors and at serotonin receptors. Unlike newer antidepressants, it is less selective. Imipramine has a long half-life of 19 hours. Antidepressant effects are delayed, occurring after one to three weeks.
Indications
- Depression
- Chronic pain
- Enuresis nocturna (bedwetting)
Dosage
According to the professional information. Therapy is started gradually and the dose is adjusted individually. Medications are usually taken one to three times daily, independent of meals. Discontinuation should be gradual.
Contraindications
- Hypersensitivity
- Combination with MAO inhibitors
- Congenital prolongation of the QT interval
- Fresh myocardial infarction
- Untreated narrow-angle glaucoma
- Paralytic intestinal obstruction
- Pyloric stenosis
- Acute urinary retention
- Prostate enlargement with residual urine formation
- Acute intoxication with alcohol, barbiturates or opioids.
- Acute delirium
- Lactation
Full precautions can be found in the drug label.
Interactions
Imipramine is a substrate of CYP3A4, CYP2C19, CYP1A2, and CYP2D6. It has a high potential for drug-drug interactions, for example, with MAO inhibitors, anticholinergics, sympathomimetics, serotonergic drugs, antihypertensives, antiarrhythmics, neuroleptics, and central depressant drugs.
Adverse effects
The most common possible adverse effects include tremor, sinus tachycardia, ECG changes, orthostatic hypotension, flushing, dry mouth, constipation, and sweating.
