Imipramine

Mechanism of action

⇄Serotonin transporter (SERT) and noradrenaline transporter (NET)Imipramine

ⓘ The figure shows imipramine bound to the human serotonin transporter (cryo-EM; vilazodone and an antibody fragment are also present).

Imipramine, a tertiary-amine tricyclic, blocks the reuptake of both serotonin and noradrenaline; it also has an active metabolite that lasts longer than the parent drug. More transmitter stays in the synapse and receptors adapt over weeks, which relieves depression. It also blocks muscarinic, histamine H1 and alpha-1 receptors and cardiac sodium channels: dry mouth, sedation, orthostatic hypotension and, in overdose, arrhythmias. How it reduces bedwetting is not fully explained.

1. Blocks serotonin and noradrenaline reuptake
2. An active metabolite prolongs the effect
3. Receptor adaptation over weeks relieves depression
4. Off-target: muscarinic, H1, alpha-1 block and Na+ channels

Indications

• Depression Major depressive disorder →
• Bedwetting in children (tablets only) Nocturnal enuresis →
• Off-label: panic disorder Panic disorder →

Adverse effects

Common

• Dry mouth, constipation and difficulty passing urine
• Drowsiness, tiredness, nightmares
• Dizziness on standing
• Sweating; appetite or weight change
• Changes in sex drive or ability

Contraindications

• MAO inhibitors now or within the previous two weeks
• Recent heart attack
• Generally avoided in people aged 65 or older

Key interactions

MAO inhibitors, linezolid, methylene blue

Serotonin syndrome and severe reactions; not combined.

Cimetidine

Raises imipramine levels.

Alcohol

More drowsiness.

Tobacco smoking

May reduce its effect.

What is monitored

• Mood, agitation and suicidal thoughts, especially early
• Pulse, blood pressure and ECG when there is heart disease
• Eye examination before starting
• Signs of infection or jaundice

Administration and safety

• Oral; for bedwetting it is given about an hour before bedtime.
• Started low and raised gradually; not stopped suddenly.
• Kept out of children's reach: a small number of tablets can be fatal.

Pregnancy and breastfeeding

Pregnancy or plans for pregnancy are discussed with the prescriber; it is used only when the benefit justifies the possible risk.

Nursing care

• Before: screen for heart disease, glaucoma, urinary retention, seizures and MAOI use.
• During: ask about mood and suicidal thoughts; tell families what to watch for.
• Check lying and standing blood pressure; teach to rise slowly.
• Teach sun protection and to avoid alcohol.

Pharmacokinetics

Absorption

Oral.

Metabolism

Liver, to an active metabolite with a longer half-life.

Onset and duration

Benefit in depression may take one to three weeks or longer.

Test yourself

Think of the answer, then tap the question to see it.

Add to my cards (3)

More Pharmacology questions →

Connections

← Back to the class: Tricyclic antidepressants (TCAs)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Imipramine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Cryo-EM structure of the wild-type human serotonin transporter complexed with vilazodone, imipramine and 15B8 Fab (RCSB Protein Data Bank, 2021); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Send

Representative model, for educational purposes only.