Desipramine

Summary

Desipramine (CHEMBL72) is an approved small-molecule adrenergic uptake inhibitor (ATC N06AA01) targeting SLC29A4, KCNJ6, and KCNJ5; indicated across 12 conditions including major depressive disorder and depressive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06AA01
• Targets: 5 (SLC29A4, KCNJ6, KCNJ5…)
• Indications: 12 conditions
• Clinical trials: 30
• Chemistry: 266.4 Da · C18H22N2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL72
Name	Desipramine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2995
ChEBI	CHEBI:47781
ATC	N06AA01
Molecular formula	C18H22N2
Molecular weight	266.4
InChIKey	HCYAFALTSJYZDH-UHFFFAOYSA-N

SMILES: CNCCCN1C2=CC=CC=C2CCC3=CC=CC=C31

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

ChEBI definition: A dibenzoazepine consisting of 10,11-dihydro-5H-dibenzo[b,f]azepine substituted on nitrogen with a 3-(methylamino)propyl group.

Pharmacological roles (ChEBI): adrenergic uptake inhibitor, serotonin uptake inhibitor, cholinergic antagonist, α-adrenergic antagonist, H1-receptor antagonist, EC 3.1.4.12 (sphingomyelin phosphodiesterase) inhibitor, EC 3.4.21.26 (prolyl oligopeptidase) inhibitor, antidepressant, drug allergen.

Also known as: Desipramina, Desipramine, Imipramine, Monodemethylimipramine, N-desmethylimipramine, Norimipramine, desipramine, Desmethylimipramine, SID11111066, SID11111067, SID90341801, SID50100220

Parent form; salt/anhydrous children: CHEMBL227644, CHEMBL1696

Patent coverage: 9,406 distinct patent families (34,909 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 34,866 (100%) 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
SLC29A4	Plasma membrane monoamine transporter	Inhibition	4.49	0.7%	Q7RTT9
KCNJ6	Kir3.2	Antagonist	4.4	0.1%	P48051
KCNJ5	Kir3.4	Antagonist	4.3	0%	P48544
SLC6A2	NET	Inhibition	8.68	0.4%	P23975
SLC6A4	SERT	Inhibition	6.79	0.7%	P31645

Broader ChEMBL bioactivity targets: 48 (assay-derived). Sample: Thrombopoietin, Solute carrier family 22 member 2, Solute carrier family 22 member 2, Solute carrier family 22 member 3, 5-hydroxytryptamine receptor 2B, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Sodium channel protein type 5 subunit alpha, Solute carrier family 22 member 4, Solute carrier family 22 member 1.

Bioactivity

ChEMBL activities: 93 potent at pChembl ≥ 5 of 128 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P43140	9.6	IC50	0.25	nM	CHEMBL_ACT_773842
SLC6A3	9.31	Ki	0.49	nM	CHEMBL_ACT_110726
SLC6A2	9.22	Ki	0.6	nM	CHEMBL_ACT_3066015
P31390	9.1	IC50	0.8	nM	CHEMBL_ACT_773843
SLC6A2	9.08	Kd	0.83	nM	CHEMBL_ACT_3554432
SLC6A2	9.04	Ki	0.92	nM	CHEMBL_ACT_13340279
SLC6A2	9.03	IC50	0.93	nM	CHEMBL_ACT_13340344
SLC6A2	9.03	IC50	0.93	nM	CHEMBL_ACT_2535120
SLC6A2	9	Ki	1	nM	CHEMBL_ACT_1855633
SLC6A2	8.96	Ki	1.1	nM	CHEMBL_ACT_13876507
SLC6A2	8.94	Ki	1.15	nM	CHEMBL_ACT_13876473
SLC6A2	8.82	IC50	1.5	nM	CHEMBL_ACT_13468995
SLC6A2	8.74	Ki	1.8	nM	CHEMBL_ACT_27603209
SLC6A2	8.68	Ki	2.1	nM	CHEMBL_ACT_2454568
SLC6A2	8.68	Ki	2.1	nM	CHEMBL_ACT_2699942
SLC6A2	8.68	Ki	2.1	nM	CHEMBL_ACT_3303764
SLC6A2	8.68	Ki	2.1	nM	CHEMBL_ACT_6357239
SLC6A2	8.6	Ki	2.5	nM	CHEMBL_ACT_19405237
SLC6A2	8.52	Ki	3	nM	CHEMBL_ACT_24507958
SLC6A2	8.48	IC50	3.3	nM	CHEMBL_ACT_3128128
SLC6A2	8.47	IC50	3.4	nM	CHEMBL_ACT_2454511
SLC6A2	8.47	IC50	3.4	nM	CHEMBL_ACT_2522823
SLC6A2	8.47	IC50	3.4	nM	CHEMBL_ACT_2587193
SLC6A2	8.47	IC50	3.4	nM	CHEMBL_ACT_2699941
SLC6A2	8.47	IC50	3.4	nM	CHEMBL_ACT_2924987
SLC6A2	8.47	IC50	3.4	nM	CHEMBL_ACT_3005585
SLC6A2	8.47	IC50	3.4	nM	CHEMBL_ACT_3128127
SLC6A2	8.47	IC50	3.4	nM	CHEMBL_ACT_3285123
SLC6A2	8.47	Ki	3.4	nM	CHEMBL_ACT_3303763
SLC6A2	8.47	IC50	3.4	nM	CHEMBL_ACT_6357252

Target pathways

Aggregated over 5 target gene(s): SLC29A4, KCNJ6, KCNJ5, SLC6A2, SLC6A4.

Top Reactome pathways

23 total, by targets touching each:

Pathway	Targets	Genes
Transmission across Chemical Synapses	3	KCNJ5, KCNJ6, SLC6A4
Neuronal System	3	KCNJ5, KCNJ6, 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
Transport of small molecules	2	SLC29A4, SLC6A2
SLC-mediated transmembrane transport	2	SLC29A4, SLC6A2
SLC-mediated transport of neurotransmitters	2	SLC6A2, SLC6A4
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
Neurotransmitter clearance	1	SLC6A4
Disease	1	SLC6A2
Serotonin clearance from the synaptic cleft	1	SLC6A4
R-HSA-425366	1	SLC6A2
Transport of vitamins, nucleosides, and related molecules	1	SLC29A4
SLC transporter disorders	1	SLC6A2
Defective SLC6A2 causes orthostatic intolerance (OI)	1	SLC6A2
Disorders of transmembrane transporters	1	SLC6A2
Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane	1	SLC29A4

Dominant GO biological processes

GO term	Targets
neurotransmitter transport	3
obsolete monoamine transport	3
obsolete serotonin transport	2
obsolete norepinephrine transport	2
serotonin uptake	2
norepinephrine uptake	2
monoatomic cation transmembrane transport	2
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
amino acid transport	2
response to xenobiotic stimulus	2
sodium ion transmembrane transport	2

Indications & clinical

Indications

12 indications (3 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
major depressive disorder	4	MONDO:0002009	MONDO:0002009
depressive disorder	4	MONDO:0002050	MONDO:0002050
post-traumatic stress disorder	3	MONDO:0005146	EFO:0001358
gastroesophageal reflux disease	3	MONDO:0007186	EFO:0003948
alcohol abuse	3	MONDO:0002046	MONDO:0007079
cocaine dependence	2	MONDO:0005186	EFO:0002610
obstructive sleep apnea syndrome	2	MONDO:0007147	EFO:0003918
sciatica	2	MONDO:0024333	HP:0011868
Rett syndrome	2	MONDO:0010726	MONDO:0010726
erectile dysfunction	1	MONDO:0005362	EFO:0004234
neoplasm	1	MONDO:0005070	MONDO:0004992

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

Clinical trials

Total trials: 30.

Phase distribution

Phase	Trials
PHASE2	8
PHASE3	6
Not specified	6
PHASE4	5
PHASE1	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00000321	PHASE4	COMPLETED	Methamphetamine Abuse Treatment in Patients With AIDS - 1
NCT00166114	PHASE4	COMPLETED	Depression, Epinephrine, and Platelet Function
NCT00320632	PHASE4	COMPLETED	Desipramine for Improving Cellular Signaling and Decreasing Symptoms of Major Depression
NCT03548454	PHASE4	COMPLETED	Comparing Effectiveness of Duloxetine and Desipramine in Patients With Chronic Pain: A Pragmatic Trial Using Point of Care Randomization
NCT03726996	PHASE4	TERMINATED	Desipramine in Infantile Neuroaxonal Dystrophy (INAD).
NCT00004390	PHASE3	COMPLETED	Phase III Randomized Controlled Study of Morphine and Nortriptyline in the Management of Postherpetic Neuralgia
NCT00006157	PHASE3	COMPLETED	Treatment of Functional Bowel Disorders
NCT00329147	PHASE3	COMPLETED	Study Evaluating the Effects of DVS SR and Paroxetine on the Pharmacokinetics of Desipramine in Healthy Subjects
NCT00338962	PHASE3	COMPLETED	Naltrexone & SSRI in Alcoholics With Depression/PTSD
NCT00366652	PHASE3	COMPLETED	Study Evaluating the Effects of DVS SR and Duloxetine on the Pharmacokinetics of Desipramine in Healthy Subjects
NCT01265550	PHASE3	COMPLETED	A Randomized Trial of Medical and Surgical Treatments for Patients With GERD Symptoms That Are Refractory to Proton Pump Inhibitors
NCT00000212	PHASE2	COMPLETED	IV Cocaine Abuse: A Laboratory Model - 1
NCT00000245	PHASE2	COMPLETED	Evaluation of a Desipramine Ceiling in Cocaine Abuse - 1
NCT00000271	PHASE2	COMPLETED	New Approaches to Cocaine Abuse Medications (A) - 6
NCT00018200	PHASE2	COMPLETED	Effect of Antidepressants on Back Pain
NCT00964886	PHASE2	COMPLETED	Efficacy of Antidepressants in Chronic Back Pain
NCT01411085	PHASE2	COMPLETED	Risperidone and Desipramine in Alcohol Use and Schizophrenia
NCT02428478	PHASE2	COMPLETED	Effect of Desipramine on Genioglossus Muscle Activity in Healthy Adults Study A
NCT02436031	PHASE2	COMPLETED	Effect of Desipramine on Upper Airway Collapsibility and Genioglossus Muscle Activity in Patients With Obstructive Sleep Apnea - Study B
NCT00500721	PHASE1	COMPLETED	Study Evaluating the Pharmacokinetics of the Potential Drug Interaction Between HCV-796 and Desipramine
NCT01358968	PHASE1	COMPLETED	A Drug Interaction Study to Assess the Effect of LY2603618 on the Metabolic Pathway of Desipramine
NCT01415128	PHASE1	COMPLETED	Compare the Pharmacokinetics of Omeprazole, Rosiglitazone, and Desipramine When Administered With Avanafil in Healthy Male Subjects
NCT01478568	PHASE1	COMPLETED	To Evaluate the Effect of Mirabegron (YM178) on Blood Levels of Desipramine When They Are Taken Together
NCT02273466	PHASE1	COMPLETED	Pharmacokinetics of Oral Desipramine With and Without Concomitant Administration of Crobenetine Infusion in Healthy Male Subjects
NCT00000376	Not specified	COMPLETED	Cognitive and Drug Therapy for Drug-Resistant Depression
NCT00018733	Not specified	COMPLETED	Biological Aspects of Depression and Antidepressant Drugs
NCT00220844	Not specified	TERMINATED	Tricyclic Antidepressants (TCAs) on Gastric Emptying
NCT00456014	Not specified	COMPLETED	Pre-Treatment Positron Emission Topography Scanning for Increasing Success in Antidepressant Treatment
NCT00880594	Not specified	TERMINATED	Irritable Bowel Syndrome (IBS) Functional Magnetic Resonance Imaging (fMRI) With Desipramine
NCT01899326	Not specified	TERMINATED	Desipramine Hydrochloride and Filgrastim For Stem Cell Mobilization in Patients With Multiple Myeloma Undergoing Stem Cell Transplant

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (1) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for desipramine and CYP2D6	CPIC	CYP2D6	yes	yes

PharmGKB also curates 5 clinical and 27 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.

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

Molecule	Source	Status	Shared targets
Fluoxetine	ChEMBL + PubChem	Phase 4 (approved)	SLC29A4, SLC6A2, SLC6A4
Imipramine	ChEMBL + PubChem	Phase 4 (approved)	KCNJ5, SLC6A2, SLC6A4
Mefloquine	ChEMBL + PubChem	Phase 4 (approved)	KCNJ5, SLC6A2, SLC6A4
Propafenone	ChEMBL + PubChem	Phase 4 (approved)	KCNJ5, SLC6A2, SLC6A4
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
Olodaterol	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
Quinidine	ChEMBL + PubChem	Phase 4 (approved)	SLC29A4, SLC6A4
Quinine	ChEMBL + PubChem	Phase 4 (approved)	SLC29A4, SLC6A4
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
Tadalafil	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
TAFENOQUINE	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
UMECLIDINIUM	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
Verapamil	ChEMBL + PubChem	Phase 4 (approved)	SLC29A4, SLC6A4
VORAPAXAR	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
ALECTINIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
AMBENONIUM	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
AMIODARONE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
AMOXAPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
ASENAPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
ATOMOXETINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
ATRACURIUM	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
AZELASTINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BENFLUOREX	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BENZPHETAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BENZTROPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BENZYDAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BEPRIDIL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BOSUTINIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BROMHEXINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BROMODIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BROMPERIDOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BROMPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BUPROPION	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BUTENAFINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CABERGOLINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CALCIPOTRIENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CALCITRIOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CARBINOXAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CARVEDILOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CELECOXIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CETIRIZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CHLORPHENTERMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CINACALCET	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CINNARIZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CITALOPRAM	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CLEMASTINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CLOMIPHENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4