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Imipramine chemical structure

IUPAC name
CAS number
ATC code


Chemical formula {{{chemical_formula}}}
Molecular weight 280.407
Bioavailability ?
Metabolism Hepatic
Main active metabolite desipramine
Elimination half-life 11-25 hours
Excretion Renal
Pregnancy category
Known risk of damage to fetus.
Legal status Rx-only
Routes of administration Oral

Imipramine (sold as Antideprin, Deprenil, Deprimin, Deprinol, Depsonil, Dynaprin, Eupramin, Imipramil, Irmin, Janimine, Melipramin, Surplix, Tofranil) is an antidepressant medication, a tricyclic antidepressant of the dibenzazepine group. Imipramine is mainly used in the treatment of major depression and enuresis.


Imipramine was, in the late 1950s, the first tricyclic antidepressant to be developed (by Ciba-Geigy). Initially, it was tried against psychotic disorders (e.g. schizophrenia), but proved insufficient. Imipramine is in fact well known to induce and exacerbate psychosis. [How to reference and link to summary or text] During the clinical studies its antidepressant qualities were unsurpassed by other antidepressants. To this day, Imipramine is often considered the "Gold Standard" antidepressant as its ability to lift the most severe depressive episodes is unsurpassed. Not surprisingly, Imipramine is also known to cause a high rate of manic and hypomanic reactions, especially in patients with preexisting bipolar disease. It is estimated that up to 25% of such patients maintained on Imipramine will switch into mania or hypomania [1]. Such powerful antidepressant properties have made it favorable in the treatment of Treatment-resistant depression.

At the advent of SSRIs, its sometimes intolerable side effect profile became evident. Subsequently, it was extensively used as a standard antidepressant and later served as a prototypical drug for the development of the later released tricyclics. It is not as commonly used today, but is sometimes used to treat major depression as a second-line treatment. It has also seen limited use in the treatment of migraines, ADD and post concussive syndrome. Imipramine has additional indications for the treatment of panic attacks, chronic pain, and Kleine-Levin syndrome. In pediatric patients it is relatively frequently used to treat pavor nocturnus and nocturnal enuresis.

Mechanisms Of Action

Imipramine, a tertiary amine, affects numerous neurotransmitter systems know to be involved in the etiology of depression, anxiety , ADD/ADHD, enuresis and numerous other mental and physical conditions. Imipramine is similar in structure to some muscle relaxants, and has a significant analgesic effect and thus is very useful in some pain conditions.

The mechanisms of Imipramine's medicinal action all include, but are not limited to effects on; norepinephrine, serotonin, dopamine, epinephrine, opiates, enkephalinase, histamine, muscarine, and acetylcholine.

Effects on;

Norepinephrine(NE) -Reuptake inhibition (strong).

Serotonin(SE) -Reuptake inhibition (moderate to strong). The reuptake inhibition is almost comparable but still less than Imipramine's potency of reuptake inhibition on norepinephrine. Stronger SERT inhibition than most other tricyclic antidepressants, making it more akin to the SSRI class of antidepressants (e.g. Prozac(fluoxetine), Zoloft (sertraline)) than its metabolite desipramine, which has almost purely noradrenergic effects.

Acetylcholine(ACh) Imipramine is an anticholinergic. Thus, it is prescribed with caution to the elderly and with extreme caution to those with pyschosis, as the general brain activity enhancement in combination with the "dementing" effects of anti-cholinergices increases the potential of Imipramine to cause hallucinations, confusion and delirium in this population. Imipramine is an antagonist at M2 muscarinic acetylcholine receptors (see external links). The blockade of (cholinergic) muscarine receptors is known to cause euphoria, potentially contributing to the mood lifting effects of Imipramine as well. Antimuscarinic effect is also responsible for rapid heart rate(tachycardia)

Epinephrine Imipramine antagonizes adreno-receptors (II), thus sometimes causing increased heart rate (contributed to by other effects as well), orthostatic hypotension, and a general decrease in the responsiveness of the central nervous system (hence, a contribution to its potent anti-anxiety properties).

Dopamine - reuptake and release at D1 and D2 receptors. similar to but less potent than the psychostimulants, dopamine agonists and atypical antidepressant buproprion on dopaminergic mechanisms. (increase in release and blockade of reutpake inhibition). While this effect is much less than the primary effects on NE, SE and ACe, it is none-the-less significant and is partially responsible for the therapeutic benefits of treatment with Imipramine. Enhancement of brain dopamine activity has been implicated in Imipramine's ability to stimulate motor activity and prolong time spent in escape in mice. In regards of dopamine uptake, imipramine is far less potent then most of other antidepressant (for example is 1/20 in potency of amitryptiline and paroxetine, see references)

Opiates and Enkephalinase Activity on opiate (sigma ligands) is present, but it is very low (Ki of 520 nM on sigma receptors, see references) and it is about half the power of amitryptiline (300 nM)

Histamine -Imipramine is an antagonist at histamine H1 receptors. This contributes to the acute sedative effect that it has in most people. In turn, its anti-histaminergic and general calming effects take place immediately and thus, Imiparmine is sometimes prescribed as a sleep aid in low doses.

Comparison with other antidepressant

The potency (affinity) of imipramine and other antidepressant on various transporters and receptors are summarized below. Data are from "Pharmacology of antidepressant", Mayo Clin Proc, May 2001, Vol 76. Potency (affinity) data ere expressed as the inverse of equilibrium dissocation constant multiplied by a factor of 10^-7. So, the higher the number, the higher the blocking power.

Drug NE Transporter SE Transporter DE transporter alpha1 blockade D2 blockade H1 blockade muscarinic blockade 5HT2 blockade
imipramine 2.7 70 0.012 1.5 0.05 9.1 1.1 1.2
desipramine (also an imipramine metabilite) 128 5.7 0.024 0.77 0.03 0.91 0.5 0.38
amitriptyline 2.9 23 0.023 3.7 0.1 91 5.6 3.4
clomipramine 2.7 360 0.045 2.6 0.53 3.2 2.7 3.7
paroxetine 2.5 800 0.2 0.025 0.003 0.03 0.93 0.005
citalopram 0.035 98 0.0038 0.053 0 0.21 0.045 0.34


Imipramine is converted to desipramine, another TCA, in the body.

Contraindications and precautions

See Tricyclic antidepressants

Imipramine should not be given in conjunction with, or within 14 days of treatment with a MAO inhibitor. Combined therapy of this type could lead to the appearance of serious interactions such as hypertensive crises, hyperactivity, hyperpyrexia, spasticity, severe convulsions or coma and death may occur.

Imipramine is contraindicated in patients with existing severe hepatic or renal damage, and those with a history of blood dyscrasias.

Imipramine is contraindicated in patients who have shown hypersensitivity to the drug or hypersensitivity to tricyclic antidepressants belonging to the dibenzazepine group.

Imipramine is contraindicated for use during the acute recovery phase following a myocardial infarction.

It should not be used in patients with convulsive disorders or glaucoma.


Side effects

After taking the medicine this drug may cause some side effects in some patients, particularly with the first few doses.

Allergic effects

Isolated cases of pneumonitis (fever, chills, cough, difficulty with breathing, unusual weight loss, feeling sick) have been reported. A puffy, swollen face, tongue or body has been reported. These reactions may be severe, causing shortness of breath, swelling, shock and collapse. If you develop any allergic symptoms, stop taking the medicine and contact your doctor immediately.

Effects on the blood

Isolated changes in blood cells. If you notice that you are bruising more frequently or have more nosebleeds or infections you should consult your doctor.

Effects on the heart

Arrhythmias: Irregular heart rhythms.

Effects on the endocrine system and metabolism

Weight gain has been reported frequently. Disturbances in sexual function have been reported occasionally. Isolated cases of enlarged mammary glands, production or over-production of breast milk, increased or decreased blood sugar levels and weight loss have been reported. Low levels of salt in the blood have been reported, usually in elderly patients, which can be identified by a blood test.

Effects on the brain and central nervous system

Tremor has been reported frequently. Headache, confusion, orthostatic hypotension (resulting in dizziness upon standing), numbness/tingling, agitation, anxiety, restlessness, mood swings, exaggerated behaviour, delusions and hallucinations have been reported occasionally and are more common in the elderly or in patients on high doses. Aggressiveness, weakness, lack of co-ordination, sudden muscle spasms, difficulty speaking have been reported in isolated cases.

Imipramine also enhances the CNS effects of both stimulants and alcohol, and blocks the parasympathomimetic effects of stimulants while enhancing the cortical excitation. This can be dangerous in some cases and result in seizures and coma.

Effects on the ears

Ringing or buzzing in the ears have been reported.

Effects on the stomach and intestines

Feeling or being sick and loss of appetite have been reported occasionally. Isolated cases of tongue lesions and inflammation of the mucus membranes in the mouth have been reported. Extreme dry mouth or "cotton mouth" has been reported. Mild to severe constipation has also been reported.

Effects on the liver

Changes in liver function have been reported occasionally. This would be identified by a blood test. Hepatitis and jaundice (yellowing of the skin and/or whites of the eyes) have been reported in isolated cases.

Effects on the skin

Allergic reactions such as an itchy skin rash have been reported occasionally. Isolated cases of swelling, sensitivity to the sun or sun lamps, hair loss, small purple red spots and itching have been reported.


If the medicine is stopped too quickly, there is the possibility the user may suffer from feeling or being sick, stomach pains, diarrhea, headache, sleeplessness, nervousness, anxiety, irritability and increased sweating.sadar


  • Hospitalized patients: starting with 3 time 25 mg, increasing to 200 mg. Up to 300 mg may be given in resistant cases. After remission dose is often reduced to 50–100 mg daily.
  • Ambulatory patients: starting with 25 to 75 mg daily, increasing up to a maximum of 200 mg daily, after remission dose is often reduced to 50–100 mg daily.
  • Pediatric patients: starting with 10 mg daily the dose is adjusted according to the severity of the symptoms to be treated, the side-effects encountered and the weight of the patient.


Main article: Tricyclic antidepressant overdose

The symptoms and the treatment of an overdose are largely the same as for the other tricyclic antidepressants. Cardinal symptoms are cardiac (tachycardia, widened QRS complex) and neurological disturbances. Any ingestion by children should be considered as serious and potentially fatal.


  • Pharmacology of Antidepressants, Mayo Clin Proc, May 2001 Vol 76
  • Opiates Ligands

External links

Antidepressants (ATC N06A) edit
Monoamine oxidase inhibitors (MAOI) Harmaline, Iproclozide, Iproniazid, Isocarboxazid, Nialamide, Phenelzine, Selegiline, Toloxatone, Tranylcypromine
Reversible inhibitor of monoamine oxidase A (RIMA) Brofaromine, Moclobemide
Dopamine reuptake inhibitor (DARI) Amineptine, Phenmetrazine, Vanoxerine, Modafinil
Norepinephrine-dopamine reuptake inhibitors Bupropion
Norepinephrine reuptake inhibitor (NRI) or (NARI) Atomoxetine, Maprotiline, Reboxetine, Viloxazine
Serotonin-norepinephrine reuptake inhibitor (SNRI) Duloxetine, Milnacipran, Venlafaxine
Selective serotonin reuptake inhibitor (SSRI) Alaproclate, Etoperidone, Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Zimelidine
Selective serotonin reuptake enhancer (SSRE) Tianeptine
Tricyclic antidepressants (TCA) Amitriptyline, Amoxapine, Butriptyline, Clomipramine, Desipramine, Dibenzepin, Dothiepin, Doxepin, Imipramine, Iprindole, Lofepramine, Melitracen, Nortriptyline, Opipramol, Protriptyline, Trimipramine
Tetracyclic antidepressants Maprotiline, Mianserin, Nefazodone, Trazodone
Noradrenergic and specific serotonergic antidepressant (NaSSA) Mirtazapine
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