ContaminantDB: Imipramine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (34)XML

Record Information

Version

1.0

Creation Date

2009-07-21 20:26:57 UTC

Update Date

2016-11-09 01:08:42 UTC

Accession Number

CHEM002199

Identification

Common Name

Imipramine

Class

Small Molecule

Description

Imipramine, the prototypical tricyclic antidepressant (TCA), is a dibenzazepine-derivative TCA. TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, imipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, imipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as imipramine and amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H₁ receptors, α₁-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. Imipramine has less sedative and anticholinergic effects than the tertiary amine TCAs, amitriptyline and clomipramine. See toxicity section below for a complete listing of side effects. Imipramine may be used to treat depression and nocturnal enuresis in children. Unlabeled indications include chronic and neuropathic pain (including diabetic neuropathy), panic disorder, attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD).

Contaminant Sources

FooDB Chemicals
STOFF IDENT Compounds
Suspected Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Adrenergic Uptake Inhibitor
Amine
Antidepressive Agent, Tricyclic
Drug
Food Toxin
Metabolite
Norepinephrine Reuptake Inhibitor
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
10,11-Dihydro-N,N-dimethyl-5H-dibenz[b,F]azepine-5-propanamine	ChEBI
3-(5H-DIBENZO[b,F]azepin-5-yl)-N,N-dimethylpropan-1-amine	ChEBI
5-[3-(Dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,F]azepine	ChEBI
Antideprin	ChEBI
Imipramin	ChEBI
Imipraminum	ChEBI
Imizine	ChEBI
Irmin	ChEBI
Melipramine	ChEBI
N-(gamma-Dimethylaminopropyl)iminodibenzyl	ChEBI
Tofranil	Kegg
N-(g-Dimethylaminopropyl)iminodibenzyl	Generator
N-(Γ-dimethylaminopropyl)iminodibenzyl	Generator
Berkomine	HMDB
Chimoreptin	HMDB
Declomipramine	HMDB
Dimipressin	HMDB
DPID	HMDB
Dyna-zina	HMDB
Dynaprin	HMDB
Eupramin	HMDB
Feinalmin	HMDB
Imavate	HMDB
Imidobenzyle	HMDB
Imilanyle	HMDB
Janimine	HMDB
Lofepramine	HMDB
Melipramin	HMDB
Psychoforin	HMDB
Surmontil	HMDB
Surplix	HMDB
Teperine	HMDB
Timolet	HMDB
Tofranil base	HMDB
Tofranil-PM	HMDB
Trimipramine maleate	HMDB
Imipramine hydrochloride	HMDB
Norchlorimipramine	HMDB
Imipramine monohydrochloride	HMDB
Imizin	HMDB
Pryleugan	HMDB
4,4'-Methylenebis(3-hydroxy-2-naphthoic acid)-3-(10,11-dihydro-5H-dibenzo(b,F)azepin-5-yl)-N,N-dimethyl-1-propanamine (1:2)	HMDB
Imipramine pamoate	HMDB

Chemical Formula

C₁₉H₂₄N₂

Average Molecular Mass

280.407 g/mol

Monoisotopic Mass

280.194 g/mol

CAS Registry Number

50-49-7

IUPAC Name

(3-{2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3,5,7,11,13-hexaen-2-yl}propyl)dimethylamine

Traditional Name

(3-{2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3,5,7,11,13-hexaen-2-yl}propyl)dimethylamine

SMILES

CN(C)CCCN1C2=CC=CC=C2CCC2=CC=CC=C12

InChI Identifier

InChI=1S/C19H24N2/c1-20(2)14-7-15-21-18-10-5-3-8-16(18)12-13-17-9-4-6-11-19(17)21/h3-6,8-11H,7,12-15H2,1-2H3

InChI Key

BCGWQEUPMDMJNV-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as dibenzazepines. Dibenzazepines are compounds with two benzene rings connected by an azepine ring. Azepine is an unsaturated seven-member heterocycle with one nitrogen atom replacing a carbon atom.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Benzazepines

Sub Class

Dibenzazepines

Direct Parent

Dibenzazepines

Alternative Parents

Substituents

Dibenzazepine
Alkyldiarylamine
Tertiary aliphatic/aromatic amine
Azepine
Benzenoid
Tertiary aliphatic amine
Tertiary amine
Azacycle
Organic nitrogen compound
Organopnictogen compound
Hydrocarbon derivative
Organonitrogen compound
Amine
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

dibenzoazepine (CHEBI:47499 )
a small molecule (CPD-11438 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

EC 3.4.21.26 (prolyl oligopeptidase) inhibitor

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	174-175°C
Boiling Point	160°C at 1.00E-01 mm Hg
Solubility	18.2 mg/L (at 24°C)

Predicted Properties

Property	Value	Source
Water Solubility	0.066 g/L	ALOGPS
logP	4.53	ALOGPS
logP	4.28	ChemAxon
logS	-3.6	ALOGPS
pKa (Strongest Basic)	9.2	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	6.48 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	90.61 m³·mol⁻¹	ChemAxon
Polarizability	33.39 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0019-7490000000-3fb4d40b6a219f088ec8	Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0019-7490000000-3fb4d40b6a219f088ec8	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4i-7490000000-746fcd08b0a7d6e7bc83	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-000i-9000000000-55d924fd00e5b357ce9e	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-000i-9000000000-eb3c0ecdffc5d9d95e33	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-0ab9-9432000000-033c51459b692622ee7d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - EI-B (Unknown) , Positive	splash10-0019-7490000000-bb99ef31a755d9f6ba14	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-052r-9010000000-961429188e57c1480db8	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9000000000-6272981565b197d622f1	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - -1V, Positive	splash10-052r-9010000000-be8c371ae701a7225d13	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9000000000-6c56d64b8822a435898c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-0a4i-9000000000-2671c52504aa0680b918	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 90V, Positive	splash10-0a4i-9100000000-a756ccfcc744eec6e5ab	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0019-9050000000-ad820fcbaa90ad01f5ed	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-000i-9010000000-7b329c019f10b027904f	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-000i-9000000000-18201fd6a82e596bb8bd	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0019-9050000000-eafe5899fec7b49f5f30	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-000i-9000000000-9adbfb340afaa417fda3	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Positive	splash10-0a4r-9000000000-9bb5a8512a91de12e786	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-000i-9000000000-48bfa7137f4eaa6b17e6	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 15V, Positive	splash10-0019-9080000000-680701a3db1bd34f0e6f	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-001i-1090000000-d8b2753be1e55651ebe7	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0019-5190000000-884d5f80618ae379a408	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-000f-9420000000-655018838b0eb1b10c77	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004i-0090000000-115aa4768e53e232aa16	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-004l-1590000000-bf5870eaefcecc8340c7	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00kf-2910000000-568ea79e9375b6365408	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004i-0090000000-fa0545de4a4dc60fd062	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0543-8890000000-6cf8e84f007ce7c750f2	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	Spectrum

Toxicity Profile

Route of Exposure

Rapidly and well absorbed after oral administration. Bioavailability is approximately 43%. Peak plasma concentrations usually attained 1 - 2 hours following oral administration. Absorption is unaffected by food.

Mechanism of Toxicity

Imipramine works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin. It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter preventing or reducing the reuptake of norepinephrine and serotonin by nerve cells. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin. Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, which is thought to contribute to relieving symptoms of depression. In addition to acutely inhibiting neurotransmitter re-uptake, imipramine causes down-regulation of cerebral cortical beta-adrenergic receptors and sensitization of post-synaptic serotonergic receptors with chronic use. This leads to enhanced serotonergic transmission.

Metabolism

Exclusively metabolized by the liver. Imipramine is converted in the liver by various CYP isoenzymes (e.g. CYP1A2, CYP2D6, CYP3A4, CYP2C9) to active metabolites desipramine and 2-hydroxydesipramine. Route of Elimination: Approximately 40% of an orally administered dose is eliminated in urine within 24 hours, 70% in 72 hours. Small amounts are eliminated in feces via the biliary elimination. Half Life: Imipramine - 8-20 hours; Desipramine (active metabolite) - up to 125 hours

Toxicity Values

LD50: 355 to 682 mg/kg (oral, rat).

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older. May also be used to manage panic disorders, with or without agoraphobia, as a second line agent in ADHD, management of eating disorders, for short-term management of acute depressive episodes in bipolar disorder and schizophrenia, and for symptomatic treatment of postherpetic neuralgia.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Antagonism of the histamine H₁ and α₁ receptors can lead to sedation and hypotension. Antimuscarinic and anticholinergic side effects such as blurred vision, dry mouth, constipation and urine retention may occur. Cardiotoxicity may occur with high doses of imipramine. Cardiovascular side effects in postural hypotension, tachycardia, hypertension, ECG changes and congestive heart failure. Psychotoxic effects include impaired memory and delirium. Induction of hypomanic or manic episodes may occur in patients with a history of bipolar disorder. Withdrawal symptoms include GI disturbances (e.g. nausea, vomiting, abdominal pain, diarrhea), anxiety, insomnia, nervousness, headache and malaise.

Treatment

Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line and initiate gastric decontamination. A minimum of 6 hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary. If signs of toxicity occur at anytime during this period, extended monitoring is required. (2)

Concentrations

Not Available

External Links

DrugBank ID

DB00458

HMDB ID

HMDB0001848

FooDB ID

FDB022706

Phenol Explorer ID

Not Available

KNApSAcK ID