Systematic (IUPAC) name
Clinical data
Trade names Tofranil
AHFS/ monograph
MedlinePlus a682389
Pregnancy cat. D(US)
Known risk of damage to fetus.
Legal status Prescription only
Routes Oral
Pharmacokinetic data
Bioavailability  ?
Metabolism Hepatic
Main active metabolite desipramine
Half-life 11-25 hours
Excretion Renal
CAS number 50-49-7
ATC code N06AA02
PubChem CID 3696
DrugBank APRD00672
ChemSpider 3568 YesY
KEGG D08070 YesY
ChEBI CHEBI:47499 YesY
Chemical data
Formula C19H24N2 
Mol. mass 280.407 g/mol
SMILES eMolecules & PubChem
 YesY(what is this?)  (verify)

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

It has also been evaluated for use in panic disorder.[1]



Imipramine was, in the late 1950s, the first tricyclic antidepressant to be developed (by Ciba). It was first tried against psychotic disorders, such as schizophrenia, but proved insufficient. As an antidepressant, it did well in clinical studies and it is known to work well in even the most severe cases of depression.[2] It is not surprising, therefore, that Imipramine is also known to cause a high rate of manic and hypomanic reactions, especially in patients with preexisting bipolar disorder. It is estimated that up to 25% of such patients maintained on Imipramine will switch into mania or hypomania.[3] 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 more tolerable. Therefore, it became 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, ADHD, 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.

Mechanism of action

Imipramine, a tertiary amine, affects numerous neurotransmitter systems known to be involved in the etiology of depression, anxiety , 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 include, but are not limited to, effects on:

  • Serotonin (5-HT): Moderate to strong reuptake inhibition. Imipramine's serotonin reuptake inhibition is almost comparable but still less than its reuptake inhibition of norepinephrine. When compared to other tricyclic antidepressants (with the exception of Clomipramine) Imipramine's strong serotonin reuptake inhibition make it more akin to the SSRI class of antidepressants than its metabolite Desipramine, which has almost purely noradrenergic effects.
  • Dopamine (DA): Reuptake and release at D1 and D2 receptors. Similar but less potent than psychostimulants, dopamine agonists, and the atypical antidepressant buproprion on dopaminergic mechanisms (increase in release and blockade of reuptake inhibition). While this effect is much less than the primary effects on NE, SER and ACh, it is nonetheless 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. Regarding dopamine uptake, imipramine is far less potent than most other antidepressants (for example, it has only 5% of the potency of amitryptiline or paroxetine, see the table below).[citation needed]
  • Acetylcholine (ACh): Imipramine is an anticholinergic. Thus, it is prescribed with caution to the elderly and with extreme caution to those with psychosis, as the general brain activity enhancement in combination with the "dementing" effects of anticholinergics 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).
  • σ receptor and Enkephalinase: Activity on σ receptors is present, but it is very low (Ki of 520 nM on σ 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, Imipramine is sometimes prescribed as a sleep aid in low doses.
  • BDNF: BDNF is implicated in neurogenesis in the hippocampus, and studies suggest that depressed patients have decreased levels of BDNF and reduced hippocampal neurogenesis. It is not clear how neurogenesis restores mood, as ablation of hippocampal neurogenesis in murine models do not show anxiety related or depression related behaviours. Chronic Imipramine administration results in increased histone acetylation (which is associated with transcriptional activation and decondensed chromatin) at the hippocampal BDNF promotor, and also reduced expression of hippocampal HDAC5.[4][5]
  • μ receptor: Imipramine has been shown to increase the expression of μ-opioid receptors in rat forebrain.[6]

Comparison with other antidepressants

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.[7]

Potency (affinity) data are expressed as the inverse of equilibrium dissociation constant multiplied by a factor of 10−7. So, the higher the number, the higher the blocking power.

Drug SERT NET DAT α1 blockade D2 blockade H1 blockade muscarinic blockade 5HT2 blockade
imipramine 70 2.7 0.012 1.5 0.05 9.1 1.1 1.2
desipramine (also an imipramine metabolite) 5.7 128 0.024 0.77 0.03 0.91 0.5 0.38
amitriptyline 23 2.9 0.023 3.7 0.1 91 5.6 3.4
clomipramine 360 2.7 0.045 2.6 0.53 3.2 2.7 3.7
paroxetine 800 2.5 0.2 0.025 0.003 0.03 0.93 0.005
citalopram 98 0.035 0.0038 0.053 0 0.21 0.045 0.34


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

Side effects

Those listed in Italic text below denote common side effects. Those listed in bold text denote life-threatening side effects.[8]

  • Central Nervous System: Dizziness, drowsiness, confusion, seizures, headache, anxiety, tremors, stimulation, weakness, insomnia, nightmares, Extrapyramidal symptoms in geriatric patients, increased psychiatric symptoms, paresthesia
  • Eyes, Ears, Nose and Throat: Blurred vision, tinnitus, mydriasis
  • Gastrointestinal: Diarrhea, Dry mouth, nausea, vomiting, paralytic ileus, increased appetite, cramps, epigastric distress, jaundice, hepatitis, stomatitis, constipation, taste change
  • Genitourinary: Urinary retention, acute renal failure
  • Skin: Rash, urticaria, sweating, pruritus, photosensitivity


  • Hospitalized patients: starting with 3 times 25 mg, increasing to 125 mg. Up to 300 mg may be given in resistant cases. After remission dose is often reduced to 50 to 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.


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.

See also


  1. ^ Lepola U, Arató M, Zhu Y, Austin C (June 2003). "Sertraline versus imipramine treatment of comorbid panic disorder and major depressive disorder". J Clin Psychiatry 64 (6): 654–62. doi:10.4088/JCP.v64n0606. PMID 12823079. 
  2. ^ Healy, David: The Antidepressant Era, page 211. Harvard University Press, 1997.
  3. ^ Bottlender R, Rudolf D, Strauss A, Möller HJ (1998). "Antidepressant-associated maniform states in acute treatment of patients with bipolar-I depression". European Archives of Psychiatry and Clinical Neuroscience 248 (6): 296–300. doi:10.1007/s004060050053. PMID 9928908. 
  4. ^ Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (April 2006). "Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action". Nature Neuroscience 9 (4): 519–25. doi:10.1038/nn1659. PMID 16501568. 
  5. ^ Krishnan V, Nestler EJ (October 2008). "The molecular neurobiology of depression". Nature 455 (7215): 894–902. Bibcode 2008Natur.455..894K. doi:10.1038/nature07455. PMC 2721780. PMID 18923511. 
  6. ^ Effects of imipramine administration on mu-opioid receptor immunostaining in the rat forebrain. de Gandarias JM, Echevarria E, Acebes I, Silio M, Casis L. 1: Arzneimittelforschung. 1998 Jul;48(7):717-9
  7. ^ Richelson E (May 2001). "Pharmacology of antidepressants". Mayo Clinic Proceedings. Mayo Clinic 76 (5): 511–27. doi:10.4065/76.5.511. PMID 11357798. 
  8. ^ Skidmore-Roth, L.(ed.). (2010). Mosby's Nursing Drug Reference (23rd ed.). St. Louis, MO: Mosby Elsevier.

External links