D0461 | imipramine

Molecular Formula C19H24N2
Molecular Weight 280.4
State solid
Clearance Imipramine has a mean clearance of 1 L/h/kg. Its active metabolite, desipramine has a mean clearance of 1.8 L/h/kg [A31907].
Volume of distribution Imipramine has a high apparent volume of distribution of 10-20 L/kg [A31907]. The drug is known to accumulate in the brain at concentrations 30-40 times that in systemic circulation.
Route of elimination Imipramine is primarily excreted in the urine with less than 5% present as the parent compound [A31907]
Protein binding Imipramine is 60-96% bound to plasma proteins in circulation [A31907]. It is known to bind albumin, alpha1-acid glycoprotein, and lipoproteins.
Half life Imipramine has a mean half life of 12 h. Its active metabolite, desipramine has a mean half life of 22.5 h [A31907].
Absorption Rapidly and well absorbed (>95%) after oral administration [A31907]. The primary site of absorption is the small intestine as the basic amine groups are ionized in the acidic environment of the stomach, preventing movement across tissues. Bioavailability ranges from 29-77% due to high inter-individual variability. Peak plasma concentration is usually attained 2-6 hours following oral administration. Absorption is unaffected by food.
Trade names Tofranil
Description prototypical tricyclic antidepressant (TCA);a dibenzazepine-derivative


N06AA02 Imipramine

[N06AA] Non-selective monoamine reuptake inhibitors



[N] Nervous system

Toxicity Dose Time Species Model Method Action Positive criterion Reference
OPENING OF PERMEABILITY TRANSITION PORE (PTP) 50 µM 1 hour Human HepG2 High-content screening assay Decrease MEC 306
UNCOUPLING increase 36
MEMBRANE POTENTIAL 74.8 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
MEMBRANE POTENTIAL 50 µM 1 hour Human HepG2 High-content screening assay Decrease MEC 306
RESPIRATION 75.5 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. increase EC20 36
RESPIRATION 18.3 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. increase EC20 36
GLUCOSE GALACTOSE IC50 RATIO 91.6 ± 18.2, 84.1 ± 10.3, 1.1, 71.4 ± 22.4, 90.3 ± 11.7, 0.8 4hr H9c2 cells high-glucose–galactose cell viability assay with JC-1 mitochondrial membrane potential and ATP-depletion assays (CellTiter-Glo reagent ). glucose/galactose IC50 ratio (JC-1 IC50 in glucose, JC-1 IC50 in galactose, JC-1 glu/gla, ATP IC50 in glucose, ATP IC50 in galactose, ATP glu/gla ) 50
SWELLING 274.4 µM 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) increase EC20 36
ROS PRODUCTION 50 µM 1 hour Human HepG2 High-content screening assay Increase MEC 306

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase inhibitor 36
potassium not specified 22
Reactive oxygen species 50 µM 1 hour Human HepG2 High-content screening assay increase MEC 306
Cytochrome c > 400 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes

Aggregated GHS information provided by 8 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria by 6 of 8 companies. For more detailed information, please visit ECHA C&L website

Of the 2 notification(s) provided by 2 of 8 companies with hazard statement code(s):

H302 (50%): Harmful if swallowed [Warning Acute toxicity, oral]

H400 (50%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

P264, P270, P273, P301+P312, P330, P391, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

  • (3-{2-azatricyclo[^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl}propyl)dimethylamine 1-(3-Dimethylaminopropyl)-4,3,6,7-dibenzazepine 1-(3-Dimethylaminopropyl)-4,5-dihydro-2,3,6,7-dibenzazepine
    10,11-Dihydro-5-(3-(dimethylamino)propyl)-5H-dibenz[b,f]azepine 10,11-Dihydro-N,N-dimethyl-5H-dibenz[b,f]azepine-5-propanamine 10,11-Dihydro-N,N-dimethyl-5H-dibenz[b,f]azepine-5-propanamine
    2,2'-(3-Dimethylaminopropylimino)bibenzyl 2,2'-(3-Dimethylaminopropylimino)dibenzyl 2241983-10-6
    3-(10,11-Dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethyl-1-propanamine 3-(10,11-Dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethyl-1-propanamine # 3-(10,11-Dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine;3-(10,11-Dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine
    3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine 3-(10,11-dihydro-5h-dibenz[b,f]azepin-5-yl)propyldimethylamine 3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N-dimethyl-propan-1-amine
    3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N-dimethylpropan-1-amine 3-(5H-DIBENZO[B,F]AZEPIN-5-YL)-N,N-DIMETHYLPROPAN-1-AMINE 5,6-Dihydro-N-(3-(dimethylamino)propyl)-11H-dibenz(b,e)azepine
    5,e)azepine 5,e]azepine 5-(3-(Dimethylamino)propyl)-10,11-dihydro-5H-dibenz(b,f)azepine
    5-(3-(Dimethylamino)propyl)-10,f)azepine 5-(3-(dimethylamino)propyl)-10,11-dihydro-5H-dibenz[b,f]azepine 5-(3-Dimethylaminopropyl)-10,11-dihydro-5H-dibenzo(b,f)azepine
    5-(3-Dimethylaminopropyl)-10,f)azepine 5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,f]azepine 50-49-7
    5H-Dibenz(b, 10,11-dihydro-5-(3-(dimethylamino)propyl)- 5H-Dibenz(b, 5-(3-(dimethylamino)propyl)-10,11-dihydro- 5H-Dibenz(b,5-[3-(dimethylamino)propyl]-10,11-dihydro-mixed with ethyl alcohol
    5H-Dibenz(b,f)azepine, 10,11-dihydro-5-(3-(dimethylamino)propyl)- 5H-Dibenz(b,f)azepine, 5-(3-(dimethylamino)propyl)-10,11-dihydro- 5H-Dibenz(b,f)azepine-5-propanamine, 10,11-dihydro-N,N-dimethyl-
    5H-Dibenz(b,f)azepine-5-propanamine, 10,11-dihydro-N,N-dimethyl- (9CI) 5H-Dibenz[b, 10,11-dihydro-N,N-dimethyl- 5H-Dibenz[b, 5-[3-(dimethylamino)propyl]-10,11-dihydro-
    5H-Dibenz[b,f]azepine, 5-[3-(dimethylamino)propyl]-10,11-dihydro- 5H-Dibenz[b,f]azepine-5-propanamine, 10,11-dihydro-N,N-dimethyl- AB00053486
    AB00053486-15 AB00053486_16 AB00053486_17
    ACM50497 AK116463 AKOS016010320
    API0006755 AX8134492 Antideprin
    BPBio1_000313 BRD-K38436528-003-05-5 BRD-K38436528-003-15-4
    BRN 0256892 BSPBio_000283 BSPBio_002172
    Berkomine C07049 CAS-113-52-0
    CAS-50-49-7 CCG-36485 CCRIS 9173
    CHEBI:47499 CHEMBL11 Censtim
    Censtin Clomipramine EP Impurity B Clomipramine HCl EP Impurity B
    D08070 DB00458 DSSTox_CID_23881
    DSSTox_GSID_43881 DSSTox_RID_80080 DTXSID1043881
    Declomipramine Dimipressin DivK1c_000559
    Dpid Dyna-zina Dynaprin
    EINECS 200-042-1 Eupramin Eupramin (Salt/Mix)
    FT-0697093 G-22355 G-22355 (Salt/Mix)
    GTPL357 HMS2089G08 HSDB 3100
    IDI1_000559 Imavate Imavate (Salt/Mix)
    Imidobenzyle Imipramin Imipramina
    Imipramina [INN-Spanish] Imipramina [Italian] Imipramine (INN)
    Imipramine [INN:BAN] Imipraminum Imipraminum [INN-Latin]
    Imiprin Imizin Imizin (Salt/Mix)
    Imizine Imizine (Salt/Mix) Imizinum (Salt/Mix)
    Impramine InChI=1/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,7,12-15H2,1-2H; Intalpram
    Iramil Irmin Janimine
    Janimine (hydrochloride) KBio1_000559 KBio2_001395
    KBio2_003963 KBio2_006531 KBio3_001392
    KBioGR_000391 KBioSS_001395 L000739
    LS-60467 Lopac-I-7379 Lopac0_000702
    MCULE-9471074673 MRF-0000592 Melipramin
    Melipramine N-(.gamma.-Dimethylaminopropyl)iminodibenzyl N-(3-Dimethylaminopropyl)-o-iminodibenzyl
    N-(gamma-Dimethylaminopropyl)iminodibenzyl NCGC00015563-01 NCGC00015563-02
    NCGC00015563-03 NCGC00015563-04 NCGC00015563-05
    NCGC00015563-06 NCGC00015563-07 NCGC00015563-08
    NCGC00015563-09 NCGC00015563-10 NCGC00015563-11
    NCGC00015563-13 NCGC00024253-03 NCGC00024253-04
    NINDS_000559 NSC 169866 NSC-169866
    NSC169866 Nelipramin Norchlorimipramine
    OGG85SX4E4 ORG-2463 Oprea1_200908
    Prestwick0_000072 Prestwick1_000072 Prestwick2_000072
    Prestwick3_000072 Promiben Psychoforin
    Psychoforin (Salt/Mix) PubChem21397 Q58396
    SBI-0050680.P004 SCHEMBL34282 SK-Pramine
    SK-Pramine (Salt/Mix) SPBio_001059 SPBio_002204
    STL416211 SY246340 Spectrum2_000990
    Spectrum3_000466 Spectrum4_000016 Spectrum5_000864
    Spectrum_000915 Surplix Surplix (Salt/Mix)
    Timolet Tofranil Tofranil (Salt/Mix)
    Tofranil (TN) Tofranil (free base) Tofranil (hydrochloride)
    Tofranil base Tofranil, base Tox21_110174
    Tox21_110174_1 UNII-OGG85SX4E4 W-109253
    W0042 WLN: T C676 BN&T&J B3N1&1 ZINC20245

    DrugBank Name imipramine
    DrugBank DB00458
    CAS Number 10075-24-8, 112898-42-7, 113-52-0, 2241983-10-6, 50-49-7
    PubChem Compound 3696
    KEGG Compound ID C07049
    KEGG Drug D08070
    ChEBI 47499
    PharmGKB PA449969