- Overview
- Properties
- Genetics
- Related Genes
- Pathways
- Related Drugs
- Related Diseases
- Datasets
- Downloads/LinkOuts
Overview
| IUPAC Name: | 3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N-dimethylpropan-1-amine |
|---|---|
| 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]
Indication
For the relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older.
ATC Therapeutic Category
- N06AA:Non-selective monoamine reuptake inhibitors
Pharmacology and Interactions
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.
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.
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.
Absorption, Distribution, Metabolism, Elimination & Toxicity
Biotransformation
Exclusively hepatic. Imipramine is converted in the liver to desipramine and 2-hydroxydesipramine, both active metabolites.
Protein Binding
89–95%
Absorption
Rapidly and well absorbed after oral administration
Half Life
11–25 hours
Toxicity
Oral, rat LD50: 355 to 682 mg/kg. Toxic signs proceed progressively from depression, irregular respiration and ataxia to convulsions and death.
Chemical Properties
Chemical Formula:
C19H24N2
SMILES Code:
CN(C)CCCN1c2ccccc2CCc3c1cccc3
(Format: OpenEye Isomeric)
Molecular Weight ( average / monoisotopic )
280.4073 / 280.1939
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
Curated Information
The following genes are in curated knowledge about this drug.
| Gene | Relationship | Evidence | |
|---|---|---|---|
|
|
BDNF |
|
Publications |
|
|
CYP1A2 |
|
Publications, Pathways |
|
|
CYP2C19 |
|
Publications, Pathways, Variants |
|
|
CYP2D6 |
|
Publications, Pathways, Variants |
|
|
CYP2E1 |
|
Publications |
|
|
CYP3A4 |
|
Pathways |
|
|
FMO1 |
|
Publications |
|
|
HSPA8 |
|
Publications |
|
|
ORM1 |
|
Publications |
|
|
UGT1A4 |
|
Publications |
Non-Curated Information
A list of non-curated publications that mention this drug along with other genes is available.
Metabolizing Enzymes
Drug Targets
PharmGKB Curated Pathways
Non-Curated Information
A list of non-curated publications that mention this drug along with other drugs is available.
Drug Interactions
| altretamine | Risk of severe hypotension |
| atazanavir | Atazanavir increases the effect and toxicity of tricyclics |
| carbamazepine | The tricyclic increases the effect of carbamazepine |
| cimetidine | Cimetidine increases the effect of tricyclic agent |
| cisapride | Increased risk of cardiotoxicity and arrhythmias |
| clonidine | The tricyclic decreases the effect of clonidine |
| dihydroquinidine barbiturate | Quinidine increases the effect of tricyclic agent |
| dobutamine | The tricyclic increases the sympathomimetic effect |
| donepezil | Possible antagonism of action |
| dopamine | The tricyclic increases the sympathomimetic effect |
| duloxetine | Possible increase in the levels of this agent when used with duloxetine |
| ephedra | The tricyclic increases the sympathomimetic effect |
| ephedrine | The tricyclic increases the sympathomimetic effect |
| epinephrine | The tricyclic increases the sympathomimetic effect |
| fenoterol | The tricyclic increases the sympathomimetic effect |
| fluconazole | The imidazole increases the effect and toxicity of the tricyclic |
| fluoxetine | Fluoxetine increases the effect and toxicity of tricyclics |
| fluvoxamine | Fluvoxamine increases the effect and toxicity of tricyclics |
| galantamine | Possible antagonism of action |
| grepafloxacin | Increased risk of cardiotoxicity and arrhythmias |
| guanethidine | The tricyclic decreases the effect of guanethidine |
| isocarboxazid | Possibility of severe adverse effects |
| isoproterenol | The tricyclic increases the sympathomimetic effect |
| ketoconazole | The imidazole increases the effect and toxicity of the tricyclic |
| mephentermine | The tricyclic increases the sympathomimetic effect |
| mesoridazine | Increased risk of cardiotoxicity and arrhythmias |
| metaraminol | The tricyclic increases the sympathomimetic effect |
| methoxamine | The tricyclic increases the sympathomimetic effect |
| moclobemide | Possible severe adverse reaction with this combination |
| norepinephrine | The tricyclic increases the sympathomimetic effect |
| orciprenaline | The tricyclic increases the sympathomimetic effect |
| phenelzine | Possibility of severe adverse effects |
| phenylephrine | The tricyclic increases the sympathomimetic effect |
| phenylpropanolamine | The tricyclic increases the sympathomimetic effect |
| pirbuterol | The tricyclic increases the sympathomimetic effect |
| procaterol | The tricyclic increases the sympathomimetic effect |
| pseudoephedrine | The tricyclic increases the sympathomimetic effect |
| quinidine | Quinidine increases the effect of tricyclic agent |
| quinidine barbiturate | Quinidine increases the effect of tricyclic agent |
| rasagiline | Possibility of severe adverse effects |
| rifabutin | The rifamycin decreases the effect of tricyclics |
| rifampin | The rifamycin decreases the effect of tricyclics |
| ritonavir | Ritonavir increases the effect and toxicity of tricyclics |
| rivastigmine | Possible antagonism of action |
| salbutamol | The tricyclic increases the sympathomimetic effect |
| sibutramine | Increased risk of CNS adverse effects |
| sparfloxacin | Increased risk of cardiotoxicity and arrhythmias |
| terbinafine | Terbinafine increases the effect and toxicity of the tricyclic |
| terbutaline | The tricyclic increases the sympathomimetic effect |
| terfenadine | Increased risk of cardiotoxicity and arrhythmias |
| thioridazine | Increased risk of cardiotoxicity and arrhythmias |
| tranylcypromine | Possibility of severe adverse effects |
Curated Information
The following diseases are in curated knowledge about this drug.
| Disease | Relationship | Evidence | |
|---|---|---|---|
|
|
Attention Deficit Disorder with Hyperactivity |
|
Pathways |
|
|
Depression |
|
Publications, Variants |
|
|
Depressive Disorder, Major |
|
Pathways |
|
|
Drug Toxicity |
|
Publications, Variants |
|
|
Fibromyalgia |
|
Pathways |
|
|
Migraine without Aura |
|
Pathways |
|
|
neuropathic pain |
|
Pathways |
|
|
Poststroke depression |
|
Pathways |
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.
