- Overview
- Properties
- Genetics
- Related Genes
- Pathways
- Related Drugs
- Related Diseases
- Datasets
- Downloads/LinkOuts
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 (
)
-
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
-
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 (
)
-
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
-
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
-
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
The following genes are in curated knowledge about this drug.
| Gene | Relationship | Evidence | |
|---|---|---|---|
|
|
BDNF |
|
Publications |
|
|
CYP1A2 |
|
Publications |
|
|
CYP2C19 |
|
Publications, Variants |
|
|
CYP2D6 |
|
Publications, Variants |
|
|
CYP2E1 |
|
Publications |
|
|
FMO1 |
|
Publications |
|
|
HSPA8 |
|
Publications |
|
|
ORM1 |
|
Publications |
|
|
UGT1A4 |
|
Publications |
A list of non-curated publications that mention this drug along with other genes is available.
Drug Targets
| Gene | Description | |
|---|---|---|
| ADORA1 |
|
(source: Drug Bank) |
| SLC6A2 |
|
(source: Drug Bank) |
| SLC6A4 |
|
(source: Drug Bank) |
PharmGKB Curated Pathways
The following drugs are in curated knowledge about this drug.
| Drug | Relationship | Evidence | |
|---|---|---|---|
|
|
lidocaine |
|
Publications |
|
|
phenytoin |
|
Publications |
|
|
tamoxifen |
|
Publications |
A list of non-curated publications that mention this drug along with other drugs is available.
Drug Interactions
| Drug | Description | |
|---|---|---|
| altretamine |
|
Risk of severe hypotension (source: Drug Bank) |
| atazanavir |
|
Atazanavir increases the effect and toxicity of tricyclics (source: Drug Bank) |
| carbamazepine |
|
The tricyclic increases the effect of carbamazepine (source: Drug Bank) |
| cimetidine |
|
Cimetidine increases the effect of tricyclic agent (source: Drug Bank) |
| cisapride |
|
Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank) |
| clonidine |
|
The tricyclic decreases the effect of clonidine (source: Drug Bank) |
| dobutamine |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| donepezil |
|
Possible antagonism of action (source: Drug Bank) |
| dopamine |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| duloxetine |
|
Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank) |
| ephedra |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| ephedrine |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| epinephrine |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| fenoterol |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| fluconazole |
|
The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank) |
| fluoxetine |
|
Fluoxetine increases the effect and toxicity of tricyclics (source: Drug Bank) |
| fluvoxamine |
|
Fluvoxamine increases the effect and toxicity of tricyclics (source: Drug Bank) |
| galantamine |
|
Possible antagonism of action (source: Drug Bank) |
| grepafloxacin |
|
Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank) |
| guanethidine |
|
The tricyclic decreases the effect of guanethidine (source: Drug Bank) |
| isocarboxazid |
|
Possibility of severe adverse effects (source: Drug Bank) |
| isoproterenol |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| ketoconazole |
|
The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank) |
| mephentermine |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| mesoridazine |
|
Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank) |
| metaraminol |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| methoxamine |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| moclobemide |
|
Possible severe adverse reaction with this combination (source: Drug Bank) |
| norepinephrine |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| orciprenaline |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| phenelzine |
|
Possibility of severe adverse effects (source: Drug Bank) |
| phenylephrine |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| phenylpropanolamine |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| pirbuterol |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| procaterol |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| pseudoephedrine |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| quinidine |
|
Quinidine increases the effect of tricyclic agent (source: Drug Bank) |
| quinidine |
|
Quinidine increases the effect of tricyclic agent (source: Drug Bank) |
| rasagiline |
|
Possibility of severe adverse effects (source: Drug Bank) |
| rifabutin |
|
The rifamycin decreases the effect of tricyclics (source: Drug Bank) |
| rifampin |
|
The rifamycin decreases the effect of tricyclics (source: Drug Bank) |
| ritonavir |
|
Ritonavir increases the effect and toxicity of tricyclics (source: Drug Bank) |
| rivastigmine |
|
Possible antagonism of action (source: Drug Bank) |
| salbutamol |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| sibutramine |
|
Increased risk of CNS adverse effects (source: Drug Bank) |
| sparfloxacin |
|
Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank) |
| terbinafine |
|
Terbinafine increases the effect and toxicity of the tricyclic (source: Drug Bank) |
| terbutaline |
|
The tricyclic increases the sympathomimetic effect (source: Drug Bank) |
| terfenadine |
|
Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank) |
| thioridazine |
|
Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank) |
| tranylcypromine |
|
Possibility of severe adverse effects (source: Drug Bank) |
Curated Information
The following diseases are in curated knowledge about this drug.
| Disease | Relationship | Evidence | |
|---|---|---|---|
|
|
Depression |
|
Publications, Variants |
|
|
Drug Toxicity |
|
Publications, Variants |
Non-Curated Information
A list of non-curated publications that mention this drug along with other diseases is available.
Additional Datasets
These datasets are minimally curated and are sorted alphabetically by title.
LinkOuts
Common Searches
Search PubMed
Search Medline Plus
Search PubChem
Search CTD
Non-Curated Publications
A list of non-curated publications that mention this drug is available.
