imipramine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
substances of the imipramine group 1427 50-49-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • imipramine
  • prazepine
  • melipramine
  • imipramine hydrochloride
  • imipramine pamoate
  • imipramine HCl
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.
  • Molecular weight: 280.42
  • Formula: C19H24N2
  • CLOGP: 5.04
  • LIPINSKI: 1
  • HAC: 2
  • HDO: 0
  • TPSA: 6.48
  • ALOGS: -3.63
  • ROTB: 4

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.10 g O
0.10 g P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 1.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 5.09 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 42 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 12 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 13 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.08 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 16 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
April 16, 1959 FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Toxicity to various agents 45.41 14.18 94 6345 211672 46467951
Completed suicide 45.35 14.18 76 6363 145844 46533779
Paranoia 31.22 14.18 19 6420 10578 46669045
Hallucination, auditory 30.96 14.18 19 6420 10737 46668886
Psychotic disorder 28.12 14.18 24 6415 22597 46657026
Urinary hesitation 26.91 14.18 10 6429 1848 46677775
Stress cardiomyopathy 25.64 14.18 15 6424 7769 46671854
Angle closure glaucoma 25.54 14.18 10 6429 2129 46677494
Catatonia 23.12 14.18 11 6428 3751 46675872
Drug withdrawal syndrome 22.36 14.18 23 6416 27361 46652262
Cardio-respiratory arrest 21.02 14.18 33 6406 59836 46619787
Rheumatoid arthritis 20.74 14.18 4 6435 240211 46439412
Depression 19.91 14.18 60 6379 170044 46509579
Procedural hypotension 19.37 14.18 7 6432 1195 46678428
Pupillary reflex impaired 18.96 14.18 8 6431 2060 46677563
Antidepressant drug level above therapeutic 18.04 14.18 5 6434 360 46679263
Fascial infection 17.08 14.18 3 6436 24 46679599
Mydriasis 16.93 14.18 13 6426 10540 46669083
Tremor 16.66 14.18 44 6395 115595 46564028
Electrocardiogram QRS complex prolonged 16.64 14.18 10 6429 5439 46674184
Confusional state 16.49 14.18 54 6385 159838 46519785
Electrocardiogram QT prolonged 16.26 14.18 27 6412 51298 46628325
Overdose 15.93 14.18 40 6399 101939 46577684
Circadian rhythm sleep disorder 15.58 14.18 4 6435 215 46679408
Parkinsonism 15.47 14.18 11 6428 7937 46671686
Depressed level of consciousness 15.03 14.18 25 6414 47544 46632079
Gastric lavage 15.00 14.18 3 6436 51 46679572
Limb mass 14.44 14.18 7 6432 2487 46677136
Hyperreflexia 14.40 14.18 9 6430 5245 46674378
Electrocardiogram abnormal 14.33 14.18 10 6429 7002 46672621

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Completed suicide 81.72 19.11 76 3277 99416 29849709
Toxicity to various agents 50.54 19.11 79 3274 177104 29772021
Blepharospasm 49.94 19.11 13 3340 913 29948212
Neuroleptic malignant syndrome 47.68 19.11 27 3326 16268 29932857
Long QT syndrome 38.08 19.11 13 3340 2320 29946805
Apathy 38.02 19.11 17 3336 6215 29942910
Trismus 37.91 19.11 13 3340 2352 29946773
Dystonia 33.63 19.11 18 3335 9709 29939416
Speech disorder 33.06 19.11 25 3328 24487 29924638
Pyelitis 32.77 19.11 6 3347 78 29949047
Muscle rigidity 30.00 19.11 17 3336 10244 29938881
Overdose 28.80 19.11 41 3312 84296 29864829
Delusion 27.54 19.11 17 3336 11972 29937153
Floppy iris syndrome 24.75 19.11 6 3347 315 29948810
Hyperammonaemia 21.31 19.11 11 3342 5509 29943616
Memory impairment 20.54 19.11 23 3330 37151 29911974
Brain oedema 19.77 19.11 14 3339 12384 29936741
Serotonin syndrome 19.28 19.11 16 3337 17875 29931250
Cognitive disorder 19.16 19.11 18 3335 23672 29925453

Pharmacologic Action:

SourceCodeDescription
ATC N06AA02 NERVOUS SYSTEM
PSYCHOANALEPTICS
ANTIDEPRESSANTS
Non-selective monoamine reuptake inhibitors
FDA EPC N0000175752 Tricyclic Antidepressant
MeSH PA D018663 Adrenergic Agents
MeSH PA D018759 Adrenergic Uptake Inhibitors
MeSH PA D000928 Antidepressive Agents
MeSH PA D000929 Antidepressive Agents, Tricyclic
MeSH PA D002491 Central Nervous System Agents
MeSH PA D049990 Membrane Transport Modulators
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D014179 Neurotransmitter Uptake Inhibitors
MeSH PA D011619 Psychotropic Drugs
CHEBI has role CHEBI:35469 thymoanaleptics
CHEBI has role CHEBI:35640 adrenergic uptake inhibitors
CHEBI has role CHEBI:76779 prolyl oligopeptidase (ec 3.4.21.26) inhibitor

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Nocturnal enuresis indication 8009008
Depressive disorder indication 35489007
Neuralgia off-label use 16269008
Cataplexy off-label use 46263000
Anxiety off-label use 48694002
Narcolepsy off-label use 60380001 DOID:8986
Bulimia nervosa off-label use 78004001
Neuropathic pain off-label use 247398009
Panic disorder off-label use 371631005 DOID:594
Attention deficit hyperactivity disorder off-label use 406506008
Ocular hypertension contraindication 4210003 DOID:9282
Suicidal thoughts contraindication 6471006
Alcoholism contraindication 7200002
Bipolar disorder contraindication 13746004 DOID:3312
Electroconvulsive therapy contraindication 23835007
Alcohol intoxication contraindication 25702006
Hyperthyroidism contraindication 34486009 DOID:7998
Conduction disorder of the heart contraindication 44808001
Chronic heart failure contraindication 48447003
Disorder of cardiovascular system contraindication 49601007 DOID:1287
Paralytic ileus contraindication 55525008 DOID:8442
Schizophrenia contraindication 58214004 DOID:5419
Intestinal obstruction contraindication 81060008 DOID:8437
Epilepsy contraindication 84757009 DOID:1826
Kidney disease contraindication 90708001 DOID:557
Seizure disorder contraindication 128613002
Cerebrovascular accident contraindication 230690007
Mania contraindication 231494001
Hypomania contraindication 231496004
Disease of liver contraindication 235856003 DOID:409
Benign prostatic hyperplasia contraindication 266569009
Retention of urine contraindication 267064002
Syncope contraindication 271594007
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Surgical procedure contraindication 387713003
Angle-closure glaucoma contraindication 392291006 DOID:13550
Disorder of coronary artery contraindication 414024009
Myocardial infarction in recovery phase contraindication 418044006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.04 Basic
pKa2 5.01 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Sodium-dependent serotonin transporter Transporter INHIBITOR Kd 8.85 WOMBAT-PK CHEMBL
Sodium-dependent noradrenaline transporter Transporter INHIBITOR Kd 7.43 WOMBAT-PK CHEMBL
Potassium voltage-gated channel subfamily H member 1 Ion channel BLOCKER IC50 5.70 IUPHAR
Adenosine receptor A3 GPCR IC50 8.36 CHEMBL
Solute carrier family 22 member 1 Transporter IC50 4.77 CHEMBL
Sodium channel alpha subunits; brain (Types I, II, III) Ion channel IC50 5.44 CHEMBL
Major prion protein Surface antigen EC50 5 CHEMBL
Sigma non-opioid intracellular receptor 1 Membrane receptor Ki 6.28 WOMBAT-PK
Muscarinic acetylcholine receptor M5 GPCR Ki 7.08 WOMBAT-PK
Muscarinic acetylcholine receptor M4 GPCR Ki 6.95 WOMBAT-PK
Muscarinic acetylcholine receptor M3 GPCR Ki 7.22 WOMBAT-PK
Muscarinic acetylcholine receptor M2 GPCR Ki 8.08 WOMBAT-PK
Muscarinic acetylcholine receptor M1 GPCR Ki 7.38 WOMBAT-PK
Histamine H1 receptor GPCR IC50 7.61 WOMBAT-PK
D(3) dopamine receptor GPCR Ki 6.41 WOMBAT-PK
Alpha-2B adrenergic receptor GPCR IC50 7.10 WOMBAT-PK
Alpha-1A adrenergic receptor GPCR IC50 7.49 WOMBAT-PK
5-hydroxytryptamine receptor 2C GPCR Ki 6.80 WOMBAT-PK
5-hydroxytryptamine receptor 2A GPCR Ki 6.82 WOMBAT-PK
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.90 WOMBAT-PK
D(2) dopamine receptor GPCR Ki 6.17 WOMBAT-PK
Solute carrier family 22 member 2 Transporter IC50 5.22 WOMBAT-PK
Sodium-dependent dopamine transporter Transporter Ki 5.07 PDSP
5-hydroxytryptamine receptor 1A GPCR Ki 5.24 PDSP
Sodium-dependent serotonin transporter Transporter Ki 7.38 CHEMBL
Serotonin 2 (5-HT2) receptor GPCR Ki 7.64 CHEMBL
Dopamine receptor GPCR IC50 6.19 CHEMBL
Muscarinic acetylcholine receptor M5 GPCR IC50 6.52 CHEMBL
Sodium-dependent dopamine transporter Transporter Ki 7.38 CHEMBL
Alpha-1A adrenergic receptor GPCR IC50 8.77 CHEMBL
Adrenergic receptor alpha-2 GPCR Ki 6.59 CHEMBL
Sodium-dependent noradrenaline transporter Transporter Ki 7.92 CHEMBL
Pleiotropic ABC efflux transporter of multiple drugs Transporter IC50 4.66 CHEMBL
Transporter Transporter Ki 7.92 CHEMBL
5-hydroxytryptamine receptor 2C GPCR Ki 6.80 CHEMBL
Glutamate NMDA receptor Ion channel IC50 4.85 CHEMBL
Muscarinic acetylcholine receptor GPCR Ki 7.19 CHEMBL
Adrenergic receptor alpha-1 GPCR Ki 7.34 CHEMBL
D(2) dopamine receptor GPCR Ki 6.14 CHEMBL
Sodium-dependent serotonin transporter Transporter Ki 8.30 CHEMBL
Histamine H1 receptor GPCR IC50 10.22 CHEMBL
Serotonin (5-HT) receptor GPCR IC50 7.36 CHEMBL
G protein-activated inward rectifier potassium channel 2 Ion channel BLOCKER IC50 4.30 IUPHAR
G protein-activated inward rectifier potassium channel 4 Unclassified BLOCKER EC50 4.50 IUPHAR

External reference:

IDSource
4019785 VUID
N0000147875 NUI
D00815 KEGG_DRUG
113-52-0 SECONDARY_CAS_RN
4017862 VANDF
4017863 VANDF
4019785 VANDF
C0020934 UMLSCUI
CHEBI:47499 CHEBI
IXX PDB_CHEM_ID
CHEMBL11 ChEMBL_ID
CHEMBL1692 ChEMBL_ID
CHEMBL3989845 ChEMBL_ID
CHEMBL2105257 ChEMBL_ID
DB00458 DRUGBANK_ID
D007099 MESH_DESCRIPTOR_UI
357 IUPHAR_LIGAND_ID
793 INN_ID
1916 INN_ID
OGG85SX4E4 UNII
3696 PUBCHEM_CID
150816 RXNORM
2328 MMSL
4870 MMSL
4871 MMSL
81685 MMSL
d00259 MMSL
001498 NDDF
001499 NDDF
001500 NDDF
3378009 SNOMEDCT_US
36113004 SNOMEDCT_US
372718005 SNOMEDCT_US
4203009 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Imipramine Pamoate HUMAN PRESCRIPTION DRUG LABEL 1 0054-0273 CAPSULE 75 mg ORAL ANDA 20 sections
Imipramine Pamoate HUMAN PRESCRIPTION DRUG LABEL 1 0054-0274 CAPSULE 100 mg ORAL ANDA 20 sections
Imipramine Pamoate HUMAN PRESCRIPTION DRUG LABEL 1 0054-0275 CAPSULE 125 mg ORAL ANDA 20 sections
Imipramine Pamoate HUMAN PRESCRIPTION DRUG LABEL 1 0054-0276 CAPSULE 150 mg ORAL ANDA 20 sections
TOFRANIL HUMAN PRESCRIPTION DRUG LABEL 1 0406-9920 TABLET, SUGAR COATED 10 mg ORAL ANDA 22 sections
TOFRANIL HUMAN PRESCRIPTION DRUG LABEL 1 0406-9921 TABLET, SUGAR COATED 25 mg ORAL ANDA 22 sections
TOFRANIL HUMAN PRESCRIPTION DRUG LABEL 1 0406-9922 TABLET, SUGAR COATED 50 mg ORAL ANDA 22 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0781-1762 TABLET, FILM COATED 10 mg ORAL ANDA 19 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0781-1764 TABLET, FILM COATED 25 mg ORAL ANDA 19 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0781-1766 TABLET, FILM COATED 50 mg ORAL ANDA 19 sections
IMIPRAMINE PAMOATE HUMAN PRESCRIPTION DRUG LABEL 1 16590-963 CAPSULE 75 mg ORAL NDA 22 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42291-345 TABLET, FILM COATED 10 mg ORAL ANDA 24 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42291-346 TABLET, FILM COATED 25 mg ORAL ANDA 24 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42291-347 TABLET, FILM COATED 50 mg ORAL ANDA 24 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 49884-054 TABLET 10 mg ORAL ANDA 20 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 49884-055 TABLET 25 mg ORAL ANDA 20 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 49884-056 TABLET 50 mg ORAL ANDA 20 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50090-0035 TABLET, FILM COATED 25 mg ORAL ANDA 21 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 50090-3148 TABLET, FILM COATED 25 mg ORAL ANDA 20 sections
IMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 51655-455 TABLET, FILM COATED 50 mg ORAL ANDA 12 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 54868-1344 TABLET, FILM COATED 25 mg ORAL ANDA 20 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 54868-2221 TABLET, FILM COATED 50 mg ORAL ANDA 20 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 54868-2571 TABLET, FILM COATED 10 mg ORAL ANDA 20 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 55289-144 TABLET, FILM COATED 25 mg ORAL ANDA 19 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 55700-709 TABLET, FILM COATED 10 mg ORAL ANDA 20 sections
Imipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 55700-710 TABLET, FILM COATED 25 mg ORAL ANDA 20 sections
Imipramine Pamoate HUMAN PRESCRIPTION DRUG LABEL 1 57297-314 CAPSULE 75 mg ORAL ANDA 20 sections
Imipramine Pamoate HUMAN PRESCRIPTION DRUG LABEL 1 57297-315 CAPSULE 100 mg ORAL ANDA 20 sections
Imipramine Pamoate HUMAN PRESCRIPTION DRUG LABEL 1 57297-316 CAPSULE 125 mg ORAL ANDA 20 sections
Imipramine Pamoate HUMAN PRESCRIPTION DRUG LABEL 1 57297-317 CAPSULE 150 mg ORAL ANDA 20 sections