PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
imipramine

2D structure

Overview

Trade Names: Antideprin; Berkomine; Censtim; Censtin; DPID; Declomipramine; Dimipressin; Dyna-Zina; Dynaprin; Estraldine; Eupramin; IM; Imavate; Imidobenzyle; Imipramina; Imipramine Hcl; Imiprin; Imizin; Imizine; Imizinum; Impramine; Intalpram; Iramil; Irmin; Janimine; Melipramin; Melipramine; Nelipramin; Norfranil; Pramine; Prazepine; Presamine; Promiben; Psychoforin; Sk-Pramine; Surplix; Timolet; Tipramine; Tofranil, Base; Tofranil-Pm; Tofraniln A; Trimipramine Maleate
PharmGKB Accession Id: PA449969

Description

The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. PubChem (source: Drug Bank)

Indication

For the relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older. (source: Drug Bank)

ATC Therapeutic Category

  • N06AA:Non-selective monoamine reuptake inhibitors

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Imipramine works by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. It binds the Sodium-dependent serotonin transporter and Sodium-dependent noradrenaline transporter, preventing or reducing the reuptake of norepinephrine and serotonin by nerve cells. As norepinephrine and serotonin are used to stimulate the synapse, and depression has been linked to a lack of stimulation of the recipient neuron at a synapse, slowing the reuptake of these neurotransmitters allows them to remain in the synaptic gap longer than it normal, increasing the stimulation of the recipient neuron and relieving the symptoms of depression. However, it does not act primarily by stimulation of the central nervous system. The clinical effect is also hypothesized as being due to potentiation of adrenergic synapses by blocking uptake of norepinephrine at nerve endings. (source: Drug Bank)

Pharmacology

Imipramine is a tricyclic antidepressant with general pharmacological properties similar to those of structurally related tricyclic antidepressant drugs such as amitriptyline and doxepin. A tertiary amine, imipramine inhibits the reuptake of serotonin more so than most secondary amine tricyclics, meaning that it blocks the reuptake of neurotransmitters serotonin and noradrenaline almost equally. It is also effective in migraine prophylaxis, but not in abortion of acute migraine attack. (source: Drug Bank)

Food Interactions

Avoid St.John's Wort.
Avoid alcohol.
Avoid excessive quantities of coffee or tea (Caffeine).
Do not take fibers at the same time.
Take with food. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Exclusively hepatic. Imipramine is converted in the liver to desipramine and 2-hydroxydesipramine, both active metabolites. (source: Drug Bank)

Protein Binding

89–95% (source: Drug Bank)

Absorption

Rapidly and well absorbed after oral administration (source: Drug Bank)

Toxicity

Oral, rat LD<sub>50</sub>: 355 to 682 mg/kg. Toxic signs proceed progressively from depression, irregular respiration and ataxia to convulsions and death. (source: Drug Bank)

Isomeric SMILES Code:

CN(C)CCCN1c2ccccc2CCc3c1cccc3 (source: Drug Bank)

In-Depth Annotations (In-Depth Annotation)

  1. rs59421388 at chr22:40853554 in CYP2D6
    This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.
    Variant Name:
    CYP2D6: 3183G>A; 3271G>A
    Related Drugs:
    citalopram, codeine, desipramine, fluoxetine, fluvoxamine, gefitinib, haloperidol, imipramine, morphine, tramadol
    Related Diseases:
    Cystic Fibrosis, Depression, Hypertension, Neoplasms, Pain, Parkinson Disease, Schizophrenia
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp
  2. rs61736512 at chr22:40855078 in CYP2D6
    This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.
    Variant Name:
    CYP2D6: 1659G>A; 1747G>A
    Related Drugs:
    citalopram, codeine, desipramine, fluoxetine, fluvoxamine, gefitinib, haloperidol, imipramine, morphine, tramadol
    Related Diseases:
    Cystic Fibrosis, Depression, Hypertension, Neoplasms, Pain, Parkinson Disease, Schizophrenia
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp

Curated Annotations (Curated Annotation)

  1. rs11188072 at chr10:96509051 in CYP2C19
    Risk or phenotype-associated allele: T Phenotype: The CYP2C19*17 allele was associated with significantly increased metabolism of imipramine. Study size: 178 Study population/ethnicity: Psychiatric patients aged 18-65 with a score of greater than or equal to 17 on the Hamilton Rating Scale for Depression. Significance metric(s): p = 0.035 Type of association: PK
    Variant Name:
    part of CYP2C19*17; CYP2C19:(-3402)C>T; CYP2C19: -3402C>T
    Related Drugs:
    imipramine
    Evidence:
    PMID:19884907
  2. rs12248560 at chr10:96511647 in CYP2C19
    Risk or phenotype-associated allele: T Phenotype: The CYP2C19*17 allele was associated with significantly increased metabolism of imipramine. Study size: 178 Study population/ethnicity: Psychiatric patients aged 18-65 with a score of greater than or equal to 17 on the Hamilton Rating Scale for Depression. Significance metric(s): p = 0.035 Type of association: PK
    Variant Name:
    part of CYP2C19*17; CYP2C19:(-806)C>T; CYP2C19: -806C>T
    Related Drugs:
    imipramine
    Evidence:
    PMID:19884907
  3. rs3892097 at chr22:40854891 in CYP2D6
    The variant allele CYP2D6*4 is the main polymorphism resulting in reduced enzyme activity in Caucasians. A number of studies show that poor metabolizer (PMs:*4/*4) reqiure a lower dose of drugs which get metabolized by CYP2D6.
    Variant Name:
    CYP2D6*4
    Related Drugs:
    clomipramine, codeine, desipramine, imipramine, nortriptyline, venlafaxine
    Related Diseases:
    Drug Toxicity
    Evidence:
    PMID:16958828
    PMID:1782973
    PMID:18070221
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
BDNF
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP1A2
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C19
  • CO
  •   
  • PK
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  • CO
  •   
  • PK
  •   
  • GN
Publications, Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP2E1
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
FMO1
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
HSPA8
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
ORM1
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
UGT1A4
  •   
  •   
  • PK
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
ADORA1 Uncurated Annotation (source: Drug Bank)
SLC6A2 Uncurated Annotation (source: Drug Bank)
SLC6A4 Uncurated Annotation (source: Drug Bank)

PharmGKB Curated Pathways

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
lidocaine
  • CO
  •   
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
phenytoin
  • CO
  •   
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  •   
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
altretamine Uncurated Annotation Risk of severe hypotension (source: Drug Bank)
atazanavir Uncurated Annotation Atazanavir increases the effect and toxicity of tricyclics (source: Drug Bank)
carbamazepine Uncurated Annotation The tricyclic increases the effect of carbamazepine (source: Drug Bank)
cimetidine Uncurated Annotation Cimetidine increases the effect of tricyclic agent (source: Drug Bank)
cisapride Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
clonidine Uncurated Annotation The tricyclic decreases the effect of clonidine (source: Drug Bank)
dobutamine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
donepezil Uncurated Annotation Possible antagonism of action (source: Drug Bank)
dopamine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
duloxetine Uncurated Annotation Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank)
ephedra Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
ephedrine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
epinephrine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
fenoterol Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
fluconazole Uncurated Annotation The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank)
fluoxetine Uncurated Annotation Fluoxetine increases the effect and toxicity of tricyclics (source: Drug Bank)
fluvoxamine Uncurated Annotation Fluvoxamine increases the effect and toxicity of tricyclics (source: Drug Bank)
galantamine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
grepafloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
guanethidine Uncurated Annotation The tricyclic decreases the effect of guanethidine (source: Drug Bank)
isocarboxazid Uncurated Annotation Possibility of severe adverse effects (source: Drug Bank)
isoproterenol Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
ketoconazole Uncurated Annotation The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank)
mephentermine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
mesoridazine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
metaraminol Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
methoxamine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
moclobemide Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
norepinephrine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
orciprenaline Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
phenelzine Uncurated Annotation Possibility of severe adverse effects (source: Drug Bank)
phenylephrine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
phenylpropanolamine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
pirbuterol Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
procaterol Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
pseudoephedrine Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
quinidine Uncurated Annotation Quinidine increases the effect of tricyclic agent (source: Drug Bank)
quinidine Uncurated Annotation Quinidine increases the effect of tricyclic agent (source: Drug Bank)
rasagiline Uncurated Annotation Possibility of severe adverse effects (source: Drug Bank)
rifabutin Uncurated Annotation The rifamycin decreases the effect of tricyclics (source: Drug Bank)
rifampin Uncurated Annotation The rifamycin decreases the effect of tricyclics (source: Drug Bank)
ritonavir Uncurated Annotation Ritonavir increases the effect and toxicity of tricyclics (source: Drug Bank)
rivastigmine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
salbutamol Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
sibutramine Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)
sparfloxacin Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
terbinafine Uncurated Annotation Terbinafine increases the effect and toxicity of the tricyclic (source: Drug Bank)
terbutaline Uncurated Annotation The tricyclic increases the sympathomimetic effect (source: Drug Bank)
terfenadine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
thioridazine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
tranylcypromine Uncurated Annotation Possibility of severe adverse effects (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
Phenotype data available No genotype data Literature annotations available Not annotated
Depression
  • CO
  •   
  • PK
  • FA
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Drug Toxicity
  •   
  •   
  • PK
  •   
  • GN
Publications, Variants

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00458
ChEBI ID:
5881
KEGG Compound ID:
C07049
PubChem Compound ID:
3696
PubChem Substance ID:
9261
IUPHAR Ligand ID:
357

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

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