PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
desipramine

2D structure

Overview

Generic Names: DMI; Demethylimipramine; Desimipramine; Desimpramine; Desipramin; Desipramine Hcl; Desmethylimipramine; Dezipramine; Dimethylimipramine; Methylaminopropyliminodibenzyl; Monodemethylimipramine; Norimipramine; Norpramine
Trade Names: Pentofran; Pertofran; Pertrofane; Sertofran
PharmGKB Accession Id: PA449233

Description

A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors. PubChem (source: Drug Bank)

Indication

For relief of symptoms in various depressive syndromes, especially endogenous depression. (source: Drug Bank)

ATC Therapeutic Category

  • N06AA:Non-selective monoamine reuptake inhibitors

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Desipramine is a tricyclic antidepressant that selectively blocks reuptake of norepinephrine (noradrenaline) from the neural synapse. It also appears to impair serotonin transport. Desipramine also possesses minor anticholinergic activity, through its affinity to muscarinic receptors. Evidence also suggests that Desiprmaine binds to and down regulates histamine and beta adrenergic receptors. Tricyclic drugs are believed to act by restoring normal levels of neurotransmitters by blocking the re-uptake of these substances from the synapse in the central nervous system. (source: Drug Bank)

Pharmacology

Desipramine, a tertiary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. Desipramine is used to treat depression, pain of neuropathic origin, attention_deficit hyperactivity disorder, functional enuresis in children, panic and phobic disorder, and to manage some eating disorders. Desipramine inhibits the re-uptake of noradrenaline at the noradrenergic nerve endings and the re-uptake of serotonin (5-hydroxy tryptamine) at the serotoninergic nerve endings in the central nervous system. These two effects are considered to be the likely base of the antidepressant effect of Desipramine. The drug also has a strong anticholinergic effect and serves as an antagonist on a1 and H1 receptors. (source: Drug Bank)

Food Interactions

Avoid alcohol.
Take with food to reduce irritation, limit caffeine intake. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Desipramine is extensively metabolized in the liver and is cleared mainly by 2-hydroxylation and glucuronidation, whereas 10-hydroxylation is of minor importance. The 2-hydroxylation metabolic pathway of desipramine is under genetic control. (source: Drug Bank)

Protein Binding

15% (source: Drug Bank)

Absorption

Desipramine hydrochloride is rapidly and almost completely absorbed from the gastrointestinal tract. 90.5% (range 73-92%) of desipramine binds to plasma proteins. (source: Drug Bank)

Toxicity

Male mice: LD<sub>50</sub> = 290 mg/kg, female rats: LD<sub>50</sub> = 320 mg/kg (source: Drug Bank)

Isomeric SMILES Code:

CNCCCN1c2ccccc2CCc3c1cccc3 (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. rs2296840 at chr1:149638671 in PSMB4
    Based on an study on 284 Mexican Americans, this variant in the 5' UTR of PSMB4 is significantly associated with major depressive disorder (MDD). The results implicate that the specific UTR variation increases the risks for a T-cell dysfunction in MDD in the studied population.
    Related Drugs:
    desipramine, fluoxetine
    Related Diseases:
    Depression
    Evidence:
    PMID:18504423
  2. rs3800373 at chr6:35650454 in FKBP5
    This variant is associated with higher chance of response to anti-depressant drugs.
    Related Drugs:
    desipramine, fluoxetine, mirtazapine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:15565110
    PMID:18349090
    PMID:18597649
  3. rs1360780 at chr6:35715549 in FKBP5
    This variant is associated with higher chance of response to anti-depressant drugs.
    Related Drugs:
    desipramine, fluoxetine, mirtazapine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:15565111
    PMID:18349090
    PMID:18597649
  4. rs17244587 at chr17:43178034 in TBX21
    Based on an study on 284 Mexican Americans, this variant in the 3' UTR of TBX21 is significantly associated with major depressive disorder (MDD). The results implicate that the specific UTR variation increases the risks for a T-cell dysfunction in MDD in the studied population.
    Related Drugs:
    desipramine, fluoxetine
    Related Diseases:
    Depression
    Evidence:
    PMID:18504423
  5. 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
CREM
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CRHR1
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP1A2
  •   
  •   
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C19
  •   
  •   
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  •   
  •   
  • PK
  •   
  •   
Publications
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
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
FKBP5
  • CO
  •   
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
PDE10A
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
PDE1B
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
PDE1C
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
PDE2A
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
PDE3A
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
PDE4A
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
PDE4B
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
PDE4C
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
PDE4D
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
PDE5A
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
PDE6C
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
PDE6D
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
PDE6G
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
PDE7A
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
PDE7B
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
PDE8A
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
PSMB4
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
SLC6A2
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
SLC6A3
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
SLC6A4
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
TBX21
  •   
  •   
  •   
  •   
  •   
Variants

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

Drug Targets

Gene Description
ADRB1 Uncurated Annotation (source: Drug Bank)
ADRB2 Uncurated Annotation (source: Drug Bank)
CHRM1 Uncurated Annotation (source: Drug Bank)
CHRM2 Uncurated Annotation (source: Drug Bank)
HRH1 Uncurated Annotation (source: Drug Bank)
SLC6A2 Uncurated Annotation (source: Drug Bank)
SLC6A4 Uncurated Annotation (source: Drug Bank)
SMPD1 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
bupropion
  •   
  •   
  • PK
  •   
  •   
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)
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)
mephentermine Uncurated Annotation The tricyclic increases the sympathomimetic effect (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)
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
  • PD
  • PK
  • FA
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Depressive Disorder
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Depressive Disorder, Major
  • CO
  •   
  •   
  • FA
  • GN
Publications
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.

Curated Phenotype Datasets

These datasets are sorted alphabetically by title.

  1. Depression Scores in Mexican-Americans Treated with Fluoxetine or Desipramine
    • No genotype data
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • CO
    Submitted by Julio Licinio, MD involving desipramine, fluoxetine, and Depression
  2. Depression Scores in Mexican-Americans Treated with Fluoxetine or Desipramine - Dropouts
    • No genotype data
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • CO
    Submitted by Julio Licinio, MD involving desipramine, fluoxetine, and Depression
  3. Depression Scores in Mexican-Americans Treated with Fluoxetine or Desipramine - Terminated
    • No genotype data
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • CO
    Submitted by Julio Licinio, MD involving desipramine, fluoxetine, and Depression
  4. Drug Levels in Depressed Mexican-Americans
    • No genotype data
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • PK
    Submitted by Julio Licinio, MD involving desipramine, fluoxetine, and Depression

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. Depression in Mexican-Americans - CRHR1
  2. Genetic Variants in Tricyclic Antidepressant associated Adverse Events
  3. PDEs and Depression in Mexican-Americans
  4. Physicochemical determinants of human renal clearance
  5. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

Downloads

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LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01151
KEGG Compound ID:
C06943
PubChem Compound ID:
2995
PubChem Substance ID:
148551
IUPHAR Ligand ID:
2399

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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