Clomipramine

Summary

Clomipramine (CHEMBL415) is an approved small-molecule serotonergic antagonist (ATC N06AA04) targeting ADRA1A, KCNJ6, and KCNJ5; indicated across 7 conditions including depressive disorder and obsessive-compulsive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06AA04
• Targets: 6 (ADRA1A, KCNJ6, KCNJ5…)
• Indications: 7 conditions
• Clinical trials: 10
• Chemistry: 314.9 Da · C19H23ClN2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL415
Name	Clomipramine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2801
ChEBI	CHEBI:47780
ATC	N06AA04
Molecular formula	C19H23ClN2
Molecular weight	314.9
InChIKey	GDLIGKIOYRNHDA-UHFFFAOYSA-N

SMILES: CN(C)CCCN1C2=CC=CC=C2CCC3=C1C=C(C=C3)Cl

IUPAC name: 3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N-dimethylpropan-1-amine

ChEBI definition: A dibenzoazepine that is 10,11-dihydro-5H-dibenzo[b,f]azepine which is substituted by chlorine at position 3 and in which the hydrogen attached to the nitrogen is replaced by a 3-(dimethylamino)propyl group. One of the more sedating tricyclic antidepressants, it is used as the hydrochloride salt for the treatment of depression as well as obsessive-compulsive disorder and phobias.

Pharmacological roles (ChEBI): serotonergic antagonist, serotonergic drug, serotonin uptake inhibitor, EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor, antidepressant, anticoronaviral agent.

Also known as: Anapramine, Chlorimipramine, Clomicalm, Clomipramina, Clomipramine, NSC-169865, clomipramine, SID11110978, SID11110979, SID11113368, SID26751616, SID90340575

Parent form; salt/anhydrous children: CHEMBL1200710

Patent coverage: 7,246 distinct patent families (27,385 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 27,246 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
ADRA1A	α1A-adrenoceptor	Antagonist	8.1		P35348
KCNJ6	Kir3.2	Antagonist	4.4	0.1%	P48051
KCNJ5	Kir3.4	Antagonist	3.6	0%	P48544
SLC6A2	NET	Inhibition	7.42	0.4%	P23975
SLC6A3	DAT	Inhibition	5.66	0.2%	Q01959
SLC6A4	SERT	Inhibition	9.55	0.7%	P31645

Broader ChEMBL bioactivity targets: 68 (assay-derived). Sample: Nuclear receptor ROR-gamma, Inositol monophosphatase 1, Thrombopoietin, Muscarinic acetylcholine receptor M4, 5-hydroxytryptamine receptor 2B, Trypanothione reductase, Alpha-2A adrenergic receptor, Adrenergic receptor alpha-1, Alpha-2C adrenergic receptor, Histamine H2 receptor.

Bioactivity

ChEMBL activities: 119 potent at pChembl ≥ 5 of 154 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P43140	10.4	IC50	0.04	nM	CHEMBL_ACT_777159
SLC6A4	10.33	Ki	0.05	nM	CHEMBL_ACT_7710549
SLC6A4	10.06	IC50	0.09	nM	CHEMBL_ACT_7710548
P31390	9.7	IC50	0.2	nM	CHEMBL_ACT_777160
SLC6A4	9.55	Ki	0.28	nM	CHEMBL_ACT_15702503
SLC6A4	8.92	AC50	1.2	nM	CHEMBL_ACT_25151035
P08909	8.3	IC50	5	nM	CHEMBL_ACT_777158
P08909	8.08	Ki	8.3	nM	CHEMBL_ACT_716832
HRH1	8.01	Ki	9.83	nM	CHEMBL_ACT_7710427
SLC6A4	8	AC50	10	nM	CHEMBL_ACT_25149838
CHRM4	7.89	Ki	13	nM	CHEMBL_ACT_7710461
ADRA1A	7.81	AC50	15.4	nM	CHEMBL_ACT_25218600
HTR2C	7.75	Ki	18	nM	CHEMBL_ACT_7710541
HTR2A	7.72	Ki	19	nM	CHEMBL_ACT_7710537
P31652	7.7	IC50	20	nM	CHEMBL_ACT_413768
CHRM1	7.66	Ki	22	nM	CHEMBL_ACT_7710455
HTR2C	7.47	IC50	34	nM	CHEMBL_ACT_7710540
CHRM3	7.44	Ki	36	nM	CHEMBL_ACT_7710459
CHRM5	7.42	Ki	38	nM	CHEMBL_ACT_7710463
DRD3	7.41	AC50	39.3	nM	CHEMBL_ACT_25194239
P43140	7.4	Ki	40	nM	CHEMBL_ACT_7708269
ADRA1A	7.35	AC50	44.5	nM	CHEMBL_ACT_25137629
ADRA2B	7.34	Ki	46	nM	CHEMBL_ACT_7708277
DRD3	7.33	Ki	47	nM	CHEMBL_ACT_7708347
P19328	7.29	Ki	51	nM	CHEMBL_ACT_716830
CHRM5	7.28	IC50	53	nM	CHEMBL_ACT_7710462
P61169	7.25	Ki	56	nM	CHEMBL_ACT_716828
SLC6A2	7.23	AC50	59.1	nM	CHEMBL_ACT_25145708
SLC6A2	7.19	IC50	64.6	nM	CHEMBL_ACT_13468996
HRH1	7.18	AC50	66	nM	CHEMBL_ACT_25211993

Target pathways

Aggregated over 6 target gene(s): ADRA1A, KCNJ6, KCNJ5, SLC6A2, SLC6A3, SLC6A4.

Top Reactome pathways

33 total, by targets touching each:

Pathway	Targets	Genes
Transmission across Chemical Synapses	4	KCNJ5, KCNJ6, SLC6A3, SLC6A4
Neuronal System	4	KCNJ5, KCNJ6, SLC6A3, SLC6A4
SLC-mediated transport of neurotransmitters	3	SLC6A2, SLC6A3, SLC6A4
Neurotransmitter clearance	2	SLC6A3, SLC6A4
Neurotransmitter receptors and postsynaptic signal transmission	2	KCNJ5, KCNJ6
Activation of G protein gated Potassium channels	2	KCNJ5, KCNJ6
G protein gated Potassium channels	2	KCNJ5, KCNJ6
Inwardly rectifying K+ channels	2	KCNJ5, KCNJ6
Potassium Channels	2	KCNJ5, KCNJ6
Disease	2	SLC6A2, SLC6A3
Transport of small molecules	2	SLC6A2, SLC6A3
R-HSA-425366	2	SLC6A2, SLC6A3
SLC-mediated transmembrane transport	2	SLC6A2, SLC6A3
SLC transporter disorders	2	SLC6A2, SLC6A3
Disorders of transmembrane transporters	2	SLC6A2, SLC6A3
GABA receptor activation	2	KCNJ5, KCNJ6
GABA B receptor activation	2	KCNJ5, KCNJ6
Activation of GABAB receptors	2	KCNJ5, KCNJ6
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	2	KCNJ5, KCNJ6
Signal Transduction	1	ADRA1A
Signaling by GPCR	1	ADRA1A
Class A/1 (Rhodopsin-like receptors)	1	ADRA1A
Amine ligand-binding receptors	1	ADRA1A
Dopamine clearance from the synaptic cleft	1	SLC6A3
Serotonin clearance from the synaptic cleft	1	SLC6A4
GPCR downstream signalling	1	ADRA1A
Adrenoceptors	1	ADRA1A
G alpha (q) signalling events	1	ADRA1A
G alpha (12/13) signalling events	1	ADRA1A
GPCR ligand binding	1	ADRA1A

Dominant GO biological processes

GO term	Targets
response to xenobiotic stimulus	4
neurotransmitter transport	3
amino acid transport	3
obsolete monoamine transport	3
sodium ion transmembrane transport	3
transmembrane transport	3
potassium ion transport	2
regulation of monoatomic ion transmembrane transport	2
potassium ion import across plasma membrane	2
monoatomic ion transport	2
monoatomic ion transmembrane transport	2
dopamine uptake involved in synaptic transmission	2
norepinephrine uptake	2
neurotransmitter reuptake	2
MAPK cascade	1

Indications & clinical

Indications

7 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
depressive disorder	4	MONDO:0002050	MONDO:0002050
obsessive-compulsive disorder	3	MONDO:0008114	EFO:0004242
anxiety	3	MONDO:0011918	EFO:0005230
dementia	3	MONDO:0001627	HP:0000726
premature ejaculation	3	MONDO:0001780	EFO:0803321

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 10.

Phase distribution

Phase	Trials
PHASE3	3
Not specified	3
PHASE2	2
PHASE4	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00564564	PHASE4	COMPLETED	Quetiapine Augmentation Versus Clomipramine Augmentation of SSRI for Obsessive-compulsive Disorder Patients
NCT00254735	PHASE3	COMPLETED	Quetiapine Augmentation in Severe Obsessive Compulsive Disorder
NCT01439984	PHASE3	COMPLETED	Trial of PED-1 in Male Patients With Premature Ejaculation
NCT02374567	PHASE3	TERMINATED	Pharmacovigilance in Gerontopsychiatric Patients
NCT00004310	PHASE2	UNKNOWN	Phase II Randomized Study of Intravenous Versus Oral Clomipramine in Patients With Obsessive Compulsive Disorder
NCT01203202	PHASE2	COMPLETED	Phase 2 Trial of PED-1 and PED-2 in Male Patients With Premature Ejaculation
NCT00913952	PHASE1	COMPLETED	To Demonstrate the Relative Bioavailability of Geneva and Basel (Anafranil) 25 mg Clomipramine Hydrochloride Capsules Under Fed and Fasted Conditions
NCT01404871	Not specified	COMPLETED	Predicting Medication Response in Obsessive Compulsive Disorder
NCT01575158	Not specified	COMPLETED	Citalopram vs Clomipramine vs Placebo in Recurrent Depression
NCT01896349	Not specified	UNKNOWN	Interpersonal Psychotherapy for Treatment Resistant Depression

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (3) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of DPWG Guideline for clomipramine and CYP2D6	DPWG	CYP2D6	yes	yes
Annotation of CPIC Guideline for clomipramine and CYP2C19, CYP2D6	CPIC	CYP2C19;CYP2D6	yes	yes
Annotation of DPWG Guideline for clomipramine and CYP2C19	DPWG	CYP2C19		yes

PharmGKB also curates 8 clinical and 60 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

857 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, KCNJ5, SLC6A2, SLC6A3, SLC6A4
MEFLOQUINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, KCNJ5, SLC6A2, SLC6A3, SLC6A4
PROPAFENONE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, KCNJ5, SLC6A2, SLC6A3, SLC6A4
ACLIDINIUM BROMIDE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
Afatinib	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CHENODIOL	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
OLODATEROL	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
PODOFILOX	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
PYRAZINAMIDE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
Tadalafil	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
Vorapaxar	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
AMIODARONE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
AMOXAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
ASENAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
AZELASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
BENFLUOREX	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
BENZPHETAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
BENZTROPINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
BENZYDAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
BEPRIDIL	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
BOSUTINIB	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
BROMPERIDOL	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CABERGOLINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CALCITRIOL	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CARVEDILOL	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CINNARIZINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CITALOPRAM	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CLEMASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CLOMIPHENE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
COBIMETINIB	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
DEQUALINIUM	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
DESIPRAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
DESLORATADINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
DOBUTAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
DOMPERIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
DOTHIEPIN	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
DOXAZOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
DRONEDARONE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
DULOXETINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
EBASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4
EPALRESTAT	ChEMBL	Phase 4 (approved)	ADRA1A, SLC6A2, SLC6A3, SLC6A4