Amoxapine

Summary

Amoxapine (CHEMBL1113) is an approved small-molecule antidepressant (ATC N06AA17) targeting HTR6, HTR7, and HTR2A; indicated across 1 condition including depressive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06AA17
• Targets: 6 (HTR6, HTR7, HTR2A…)
• Indications: 1 condition
• Clinical trials: 13
• Chemistry: 313.8 Da · C17H16ClN3O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1113
Name	Amoxapine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2170
ChEBI	CHEBI:2675
ATC	N06AA17
Molecular formula	C17H16ClN3O
Molecular weight	313.8
InChIKey	QWGDMFLQWFTERH-UHFFFAOYSA-N

SMILES: C1CN(CCN1)C2=NC3=CC=CC=C3OC4=C2C=C(C=C4)Cl

IUPAC name: 8-chloro-6-piperazin-1-ylbenzo[b][1,4]benzoxazepine

ChEBI definition: A dibenzooxazepine compound having a chloro substituent at the 2-position and a piperazin-1-yl group at the 11-position.

Pharmacological roles (ChEBI): antidepressant, adrenergic uptake inhibitor, dopaminergic antagonist, serotonin uptake inhibitor, geroprotector.

Also known as: Amoxapina, Amoxapine, Asendin, Asendis, CL 67,772, CL 67772, CL-67,772, CL-67772, Defanyl, NSC-759559, amoxapine, SID11110675

Patent coverage: 5,180 distinct patent families (20,128 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 20,006 (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
HTR6	5-HT6 receptor	Antagonist	7.3	0.2%	P50406
HTR7	5-HT7 receptor	Antagonist	7.4	0.8%	P34969
HTR2A	5-HT2A receptor	Antagonist	9	0%	P28223
HTR2C	5-HT2C receptor	Antagonist	8.7	0%	P28335
SLC6A2	NET	Inhibition	7.89	0.4%	P23975
SLC6A4	SERT	Inhibition	7.74	0.7%	P31645

Broader ChEMBL bioactivity targets: 63 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Lysine-specific demethylase 4E, Ubiquitin carboxyl-terminal hydrolase 2, Survival motor neuron protein, Prelamin-A/C, Inositol monophosphatase 1, Ferritin light chain, Thrombopoietin, Endonuclease 4, Peripheral myelin protein 22.

Bioactivity

ChEMBL activities: 102 potent at pChembl ≥ 5 of 131 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2A	9.35	Ki	0.44	nM	CHEMBL_ACT_7625580
HTR2A	8.81	IC50	1.55	nM	CHEMBL_ACT_7625579
HTR2A	8.77	AC50	1.7	nM	CHEMBL_ACT_25173573
HTR2A	8.75	Ki	1.77	nM	CHEMBL_ACT_10878915
HTR2C	8.7	Ki	1.98	nM	CHEMBL_ACT_7625584
HTR2C	8.42	IC50	3.79	nM	CHEMBL_ACT_7625583
LMNA	8.3	Potency	5	nM	CHEMBL_ACT_3653418
HTR2B	8.18	Ki	6.57	nM	CHEMBL_ACT_7625582
HTR2B	8.12	AC50	7.6	nM	CHEMBL_ACT_25164076
TDP1	8	Potency	10	nM	CHEMBL_ACT_3932592
HTR2B	8	IC50	10	nM	CHEMBL_ACT_7625581
HTR2C	7.96	AC50	11	nM	CHEMBL_ACT_25131694
HRH1	7.96	Ki	11	nM	CHEMBL_ACT_7624142
SLC6A2	7.89	IC50	13	nM	CHEMBL_ACT_7622720
SLC6A2	7.89	Ki	13	nM	CHEMBL_ACT_7622721
SLC6A2	7.84	IC50	14.3	nM	CHEMBL_ACT_29265423
SLC6A4	7.75	Ki	18	nM	CHEMBL_ACT_7625592
HTR6	7.63	AC50	23.4	nM	CHEMBL_ACT_25118937
DRD4	7.47	Ki	34	nM	CHEMBL_ACT_10878895
SLC6A4	7.47	IC50	34	nM	CHEMBL_ACT_7625591
HTR6	7.46	Ki	35	nM	CHEMBL_ACT_7625590
DRD3	7.34	Ki	46	nM	CHEMBL_ACT_7624112
DRD4	7.29	AC50	51.2	nM	CHEMBL_ACT_25127354
DRD3	7.25	AC50	56	nM	CHEMBL_ACT_25193412
P15823	7.22	Ki	60	nM	CHEMBL_ACT_7622705
HRH1	7.17	AC50	67	nM	CHEMBL_ACT_25212391
DRD2	7.17	Ki	67	nM	CHEMBL_ACT_7624110
HTR6	7.12	IC50	76	nM	CHEMBL_ACT_7625589
SLC6A2	7.09	AC50	81	nM	CHEMBL_ACT_25144885
HTR2A	7.09	AC50	82	nM	CHEMBL_ACT_25225063

Target pathways

Aggregated over 6 target gene(s): HTR6, HTR7, HTR2A, HTR2C, SLC6A2, SLC6A4.

Top Reactome pathways

22 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	4	HTR2A, HTR2C, HTR6, HTR7
Signaling by GPCR	4	HTR2A, HTR2C, HTR6, HTR7
Class A/1 (Rhodopsin-like receptors)	4	HTR2A, HTR2C, HTR6, HTR7
Amine ligand-binding receptors	4	HTR2A, HTR2C, HTR6, HTR7
GPCR downstream signalling	4	HTR2A, HTR2C, HTR6, HTR7
Serotonin receptors	4	HTR2A, HTR2C, HTR6, HTR7
GPCR ligand binding	4	HTR2A, HTR2C, HTR6, HTR7
G alpha (q) signalling events	2	HTR2A, HTR2C
G alpha (s) signalling events	2	HTR6, HTR7
SLC-mediated transport of neurotransmitters	2	SLC6A2, SLC6A4
Neurotransmitter clearance	1	SLC6A4
Transmission across Chemical Synapses	1	SLC6A4
Neuronal System	1	SLC6A4
Disease	1	SLC6A2
Serotonin clearance from the synaptic cleft	1	SLC6A4
Transport of small molecules	1	SLC6A2
R-HSA-425366	1	SLC6A2
SLC-mediated transmembrane transport	1	SLC6A2
SLC transporter disorders	1	SLC6A2
Defective SLC6A2 causes orthostatic intolerance (OI)	1	SLC6A2
Disorders of transmembrane transporters	1	SLC6A2
RHOBTB3 ATPase cycle	1	HTR7

Dominant GO biological processes

GO term	Targets
chemical synaptic transmission	5
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	4
signal transduction	4
G protein-coupled receptor signaling pathway	4
G protein-coupled serotonin receptor signaling pathway	4
response to xenobiotic stimulus	3
adenylate cyclase-activating serotonin receptor signaling pathway	2
circadian rhythm	2
vasoconstriction	2
intracellular calcium ion homeostasis	2
phospholipase C-activating serotonin receptor signaling pathway	2
serotonin receptor signaling pathway	2
memory	2
positive regulation of phosphatidylinositol biosynthetic process	2
positive regulation of fat cell differentiation	2

Indications & clinical

Indications

1 indication (1 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:0002009

Clinical trials

Total trials: 13.

Phase distribution

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

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01193816	PHASE4	COMPLETED	Loxapine in the Management of Restlessness During Mechanical Ventilation Weaning
NCT03110900	PHASE4	TERMINATED	Inhaled Loxapine vs Intramuscular (IM) Haloperidol + Lorazepam for Agitation
NCT00290082	PHASE3	TERMINATED	Randomized Double-blind Trial of Midazolam and Loxapine in Agitated Patients
NCT04148963	PHASE3	UNKNOWN	A Study of Staccato Loxapine (ADASUVE®) for Inhalation
NCT05324852	PHASE3	TERMINATED	AGItated Patients Management: intraNASAL Midazolam vs Intramuscular Loxapine
NCT00489476	PHASE2	COMPLETED	Staccato Loxapine in Migraine (in Clinic)
NCT02820519	PHASE2	TERMINATED	Tolerability and Analgesic Efficacy of Loxapine in Patients With Refractory, Chemotherapy-induced Neuropathic Pain
NCT00789360	PHASE1	COMPLETED	Staccato Loxapine Pulmonary Safety in Healthy Volunteers
NCT00874237	PHASE1	COMPLETED	Staccato Loxapine Thorough QT/QTc Study
NCT00889837	PHASE1	COMPLETED	Staccato Loxapine Pulmonary Safety in Patients With COPD
NCT00122733	Not specified	COMPLETED	Loxapine and Weaning From Ventilator
NCT02600741	Not specified	COMPLETED	Family Intervention in Recent Onset Schizophrenia Treatment (FIRST)
NCT03513549	Not specified	SUSPENDED	Observational Study Evaluating the Safety of ADASUVE® in Agitation Associated With Schizophrenia or Bipolar I Disorder

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

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

Molecule	Source	Status	Shared targets
BREXPIPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
AZELASTINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
CARVEDILOL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
CINACALCET	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
CLOZAPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
DOXEPIN	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
HALOPERIDOL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
IMIPRAMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
LOXAPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
MIANSERIN	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
NEFAZODONE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
PROMAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
RISPERIDONE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
TEGASEROD	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
THIORIDAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
METERGOLINE	ChEMBL	Phase 2	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
PENFLURIDOL	ChEMBL	Phase 2	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
RITANSERIN	ChEMBL	Phase 2	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
Pyrazinamide	PubChem	Approved	HTR2A, HTR2C, HTR6, HTR7, SLC6A2, SLC6A4
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
AMIODARONE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
ASENAPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
BENZTROPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
CARIPRAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A4
CLEMASTINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
DESLORATADINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
DIBENZEPIN	ChEMBL	Phase 4 (approved)	HTR2A, HTR6, HTR7, SLC6A2, SLC6A4
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
EBASTINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
ECONAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
FLUOXETINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
HALOPROGIN	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
ILOPERIDONE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
KETANSERIN	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A4
MEPAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
METHAPYRILENE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
MICONAZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
OLANZAPINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, HTR7, SLC6A4
ORPHENADRINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
PERPHENAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR7, SLC6A2, SLC6A4
PIMOZIDE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
PIPAMAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
PROCHLORPERAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
PROMETHAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
PROPAFENONE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
PROPRANOLOL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
RALOXIFENE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR6, SLC6A2, SLC6A4
SALMETEROL	ChEMBL	Phase 4 (approved)	HTR2A, HTR2C, HTR7, SLC6A2, SLC6A4