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

Stem definitionDrug idCAS RN
substances of the imipramine group 701 303-49-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • clomipramine
  • chlorimipramine
  • clomipramine hydrochloride
  • clomipramine HCl
A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.
  • Molecular weight: 314.86
  • Formula: C19H23ClN2
  • CLOGP: 5.92
  • LIPINSKI: 1
  • HAC: 2
  • HDO: 0
  • TPSA: 6.48
  • ALOGS: -4.34
  • 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
MRTD (Maximum Recommended Therapeutic Daily Dose) 13.24 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 51 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 13 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 8.20 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.03 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 26 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 29, 1989 FDA MALLINCKRODT LLC

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
Coma 297.57 46.53 74 891 8982 2348138
Toxicity to various agents 245.97 46.53 85 880 32669 2324451
Serotonin syndrome 238.84 46.53 52 913 3488 2353632
Overdose 197.95 46.53 64 901 19843 2337277
Suicide attempt 183.45 46.53 53 912 11229 2345891
Intentional overdose 183.27 46.53 53 912 11268 2345852
Drug interaction 166.58 46.53 62 903 29101 2328019
Hypotension 128.61 46.53 53 912 32383 2324737
Confusional state 121.51 46.53 47 918 24297 2332823
Somnolence 108.87 46.53 43 922 23442 2333678
Tachycardia 104.80 46.53 38 927 16371 2340749
Acute kidney injury 104.72 46.53 44 921 28078 2329042
Neuroleptic malignant syndrome 104.11 46.53 24 941 2056 2355064
Drug abuse 100.34 46.53 34 931 11992 2345128
Poisoning deliberate 94.19 46.53 20 945 1171 2355949
Electrocardiogram QT prolonged 93.27 46.53 29 936 7785 2349335
Drug ineffective 88.17 46.53 60 905 101564 2255556
Agitation 87.28 46.53 30 935 11021 2346099
Fall 85.92 46.53 45 920 47054 2310066
Cerebellar syndrome 83.21 46.53 16 949 565 2356555
International normalised ratio abnormal 76.41 46.53 15 950 591 2356529
Hyperchloraemia 73.08 46.53 11 954 83 2357037
Polyuria 71.88 46.53 16 949 1166 2355954
Bezoar 70.96 46.53 12 953 201 2356919
Hyponatraemia 70.80 46.53 27 938 13298 2343822
Tremor 65.77 46.53 29 936 20632 2336488
Depressed level of consciousness 65.29 46.53 22 943 7582 2349538
Intentional self-injury 65.05 46.53 19 946 4108 2353012
Anxiety 61.91 46.53 31 934 29328 2327792
Akathisia 61.23 46.53 15 950 1659 2355461
Depression 57.23 46.53 29 936 28103 2329017
Sopor 56.86 46.53 17 948 3978 2353142
Drug withdrawal syndrome neonatal 55.70 46.53 11 954 446 2356674
Myoclonus 55.36 46.53 15 950 2468 2354652
Hypernatraemia 53.79 46.53 12 953 882 2356238
Product use in unapproved indication 53.42 46.53 21 944 11179 2345941
Antipsychotic drug level increased 53.30 46.53 11 954 558 2356562
Off label use 53.14 46.53 39 926 73559 2283561
Hepatitis 53.06 46.53 18 947 6319 2350801
Completed suicide 52.67 46.53 25 940 21009 2336111
Exposure during pregnancy 51.28 46.53 26 939 25193 2331927
Sinus tachycardia 51.02 46.53 15 950 3310 2353810
Suicidal ideation 50.12 46.53 20 945 11067 2346053
Muscle rigidity 50.04 46.53 13 952 1818 2355302
Constipation 48.98 46.53 24 941 21605 2335515
Hyperthermia 47.87 46.53 12 953 1456 2355664

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
Toxicity to various agents 207.29 45.20 74 563 29067 1717077
Overdose 159.15 45.20 53 584 16648 1729496
Agitation 129.11 45.20 41 596 10985 1735159
Suicide attempt 122.86 45.20 36 601 7345 1738799
Serotonin syndrome 120.58 45.20 29 608 2759 1743385
Intentional overdose 108.45 45.20 33 604 7637 1738507
Obsessive-compulsive disorder 105.83 45.20 21 616 807 1745337
Completed suicide 98.48 45.20 37 600 16275 1729869
Therapeutic product effect variable 83.05 45.20 13 624 119 1746025
Drug ineffective 82.83 45.20 50 587 63751 1682393
Akathisia 79.43 45.20 18 619 1310 1744834
Antipsychotic drug level below therapeutic 78.38 45.20 13 624 176 1745968
Cardio-respiratory arrest 78.18 45.20 27 610 9266 1736878
Coma 72.47 45.20 24 613 7238 1738906
Disinhibition 70.61 45.20 13 624 331 1745813
Euphoric mood 70.19 45.20 15 622 830 1745314
Coma scale abnormal 69.34 45.20 14 623 585 1745559
Poisoning deliberate 64.58 45.20 14 623 828 1745316
Increased appetite 62.60 45.20 14 623 957 1745187
Tremor 62.06 45.20 25 612 13106 1733038
Hyperhidrosis 59.77 45.20 24 613 12464 1733680
Neuroleptic malignant syndrome 59.47 45.20 17 620 3131 1743013
Neutrophil count increased 58.07 45.20 16 621 2577 1743567
Electrocardiogram QT prolonged 57.98 45.20 19 618 5526 1740618
Speech disorder 57.46 45.20 18 619 4530 1741614
Sopor 57.32 45.20 15 622 1986 1744158
White blood cell count increased 56.62 45.20 20 617 7292 1738852
Drug interaction 55.21 45.20 29 608 27929 1718215
Hypovolaemic shock 52.59 45.20 12 625 896 1745248
Hallucination, auditory 47.09 45.20 13 624 2104 1744040
Therapeutic product effect incomplete 46.36 45.20 16 621 5432 1740712
Loose associations 45.28 45.20 6 631 13 1746131

Pharmacologic Action:

SourceCodeDescription
ATC N06AA04 NERVOUS SYSTEM
PSYCHOANALEPTICS
ANTIDEPRESSANTS
Non-selective monoamine reuptake inhibitors
CHEBI has role CHEBI:50949 serotonin uptake inhibitor
CHEBI has role CHEBI:35469 antidepressant
CHEBI has role CHEBI:48279 serotonergic antagonist
CHEBI has role CHEBI:48278 serotonergic drug
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
MeSH PA D018490 Serotonin Agents
MeSH PA D017367 Serotonin Uptake Inhibitors
FDA EPC N0000175752 Tricyclic Antidepressant

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Obsessive-compulsive disorder indication 191736004 DOID:10933
Depressive disorder off-label use 35489007
Cataplexy off-label use 46263000
Anxiety off-label use 48694002
Panic disorder off-label use 371631005 DOID:594
Suicidal thoughts contraindication 6471006
Alcoholism contraindication 7200002
Glaucoma contraindication 23986001 DOID:1686
Hyperthyroidism contraindication 34486009 DOID:7998
Acute nephropathy contraindication 58574008
Epilepsy contraindication 84757009 DOID:1826
Bipolar affective disorder, current episode manic contraindication 191618007
Disease of liver contraindication 235856003 DOID:409
Retention of urine contraindication 267064002
Pheochromocytoma contraindication 302835009
Malignant hyperthermia contraindication 405501007
Myocardial infarction in recovery phase contraindication 418044006
Neuroblastoma contraindication 432328008 DOID:769
Atrioventricular Conduction Defect contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.04 Basic
pKa2 6.19 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 Ki 9.70 PDSP CHEMBL
Sodium-dependent noradrenaline transporter Transporter INHIBITOR Kd 7.42 WOMBAT-PK IUPHAR
5-hydroxytryptamine receptor 2A GPCR Ki 7.45 PDSP
D(1A) dopamine receptor GPCR Ki 6.66 PDSP
D(2) dopamine receptor GPCR Ki 6.95 PDSP
Alpha-2A adrenergic receptor GPCR Ki 6.28 PDSP
Sigma non-opioid intracellular receptor 1 Membrane receptor Ki 6.24 DRUG MATRIX
5-hydroxytryptamine receptor 2B GPCR Ki 6.82 DRUG MATRIX
Alpha-2B adrenergic receptor GPCR Ki 7.34 DRUG MATRIX
Histamine H1 receptor GPCR Ki 8.01 DRUG MATRIX
Histamine H2 receptor GPCR Ki 5.70 DRUG MATRIX
Muscarinic acetylcholine receptor M1 GPCR Ki 7.66 DRUG MATRIX
Muscarinic acetylcholine receptor M2 GPCR Ki 7.07 DRUG MATRIX
Muscarinic acetylcholine receptor M3 GPCR Ki 7.44 DRUG MATRIX
Muscarinic acetylcholine receptor M4 GPCR Ki 7.89 DRUG MATRIX
Muscarinic acetylcholine receptor M5 GPCR Ki 7.42 DRUG MATRIX
Alpha-2C adrenergic receptor GPCR Ki 6.69 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 7.40 DRUG MATRIX
Solute carrier family 22 member 1 Transporter IC50 4.71 CHEMBL
5-hydroxytryptamine receptor 6 GPCR Ki 6.95 CHEMBL
Sodium-dependent dopamine transporter Transporter IC50 5.56 CHEMBL
Glutathione S-transferase P Enzyme WOMBAT-PK
Cytochrome P450 2D6 Enzyme Ki 5.66 WOMBAT-PK
Aldehyde oxidase Enzyme IC50 6.32 WOMBAT-PK
Alpha-1A adrenergic receptor GPCR Ki 8.49 WOMBAT-PK
D(3) dopamine receptor GPCR Ki 7.41 PDSP
5-hydroxytryptamine receptor 2C GPCR Ki 7.19 PDSP
Alpha-1B adrenergic receptor GPCR Ki 7.14 DRUG MATRIX
Membrane-associated progesterone receptor component 1 Membrane receptor Ki 5.94 DRUG MATRIX
Trypanothione reductase Enzyme Ki 5.19 CHEMBL
Serotonin 2 (5-HT2) receptor GPCR Ki 8.08 CHEMBL
Adrenergic receptor alpha-2 GPCR Ki 7.29 CHEMBL
Alpha-1A adrenergic receptor GPCR IC50 10.40 CHEMBL
Serotonin 1 (5-HT1) receptor GPCR Ki 5.30 CHEMBL
Histamine H1 receptor GPCR IC50 9.70 CHEMBL
Serotonin (5-HT) receptor GPCR IC50 8.30 CHEMBL
Sodium-dependent noradrenaline transporter Transporter IC50 6.05 CHEMBL
D(2) dopamine receptor GPCR Ki 7.25 CHEMBL
Sodium-dependent serotonin transporter Transporter IC50 7.15 CHEMBL
Trypanothione reductase Unclassified IC50 5.47 CHEMBL
G protein-activated inward rectifier potassium channel 2 Ion channel BLOCKER IC50 4.40 IUPHAR

External reference:

IDSource
D002997 MESH_DESCRIPTOR_UI
4019687 VUID
N0000147779 NUI
C0009010 UMLSCUI
D00811 KEGG_DRUG
2LXW0L6GWJ UNII
17321-77-6 SECONDARY_CAS_RN
96209002 SNOMEDCT_US
4019687 VANDF
2597 RXNORM
004614 NDDF
372903001 SNOMEDCT_US
d00876 MMSL
CHEMBL415 ChEMBL_ID
CHEMBL1200710 ChEMBL_ID
2238 INN_ID
DB01242 DRUGBANK_ID
CHEBI:47780 CHEBI
2398 IUPHAR_LIGAND_ID
2801 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-3025 CAPSULE 25 mg ORAL ANDA 15 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-3050 CAPSULE 50 mg ORAL ANDA 15 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-3075 CAPSULE 75 mg ORAL ANDA 15 sections
CLOMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 0406-8806 CAPSULE 25 mg ORAL NDA 15 sections
CLOMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 0406-8807 CAPSULE 50 mg ORAL NDA 15 sections
CLOMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 0406-8808 CAPSULE 75 mg ORAL NDA 15 sections
ANAFRANIL HUMAN PRESCRIPTION DRUG LABEL 1 0406-9906 CAPSULE 25 mg ORAL NDA 15 sections
ANAFRANIL HUMAN PRESCRIPTION DRUG LABEL 1 0406-9907 CAPSULE 50 mg ORAL NDA 15 sections
ANAFRANIL HUMAN PRESCRIPTION DRUG LABEL 1 0406-9908 CAPSULE 75 mg ORAL NDA 15 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0781-2027 CAPSULE 25 mg ORAL ANDA 15 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0781-2037 CAPSULE 50 mg ORAL ANDA 15 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0832-0630 CAPSULE 25 mg ORAL ANDA 15 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0832-0631 CAPSULE 50 mg ORAL ANDA 15 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0832-0632 CAPSULE 75 mg ORAL ANDA 15 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 16714-849 CAPSULE 25 mg ORAL ANDA 15 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 16714-850 CAPSULE 50 mg ORAL ANDA 15 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 16714-851 CAPSULE 75 mg ORAL ANDA 15 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43063-257 CAPSULE 25 mg ORAL ANDA 15 sections
CLOMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 51672-4011 CAPSULE 25 mg ORAL ANDA 16 sections
CLOMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 51672-4012 CAPSULE 50 mg ORAL ANDA 16 sections
CLOMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 51672-4013 CAPSULE 75 mg ORAL ANDA 16 sections
CLOMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 54868-4023 CAPSULE 50 mg ORAL ANDA 16 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 59746-710 CAPSULE 25 mg ORAL ANDA 16 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 59746-711 CAPSULE 50 mg ORAL ANDA 16 sections
Clomipramine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 59746-712 CAPSULE 75 mg ORAL ANDA 16 sections
CLOMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 60429-287 CAPSULE 25 mg ORAL ANDA 16 sections
CLOMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 60429-288 CAPSULE 75 mg ORAL ANDA 16 sections
CLOMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 60429-289 CAPSULE 50 mg ORAL ANDA 16 sections
CLOMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 68084-790 CAPSULE 25 mg ORAL ANDA 16 sections
CLOMIPRAMINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 68084-818 CAPSULE 50 mg ORAL ANDA 16 sections