Loxapine

Summary

Loxapine (CHEMBL831) is an approved small-molecule antipsychotic agent (ATC N05AH01) targeting HTR6, HTR7, and DRD2; indicated across 12 conditions including psychotic disorder and bipolar disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AH01
• Targets: 9 (HTR6, HTR7, DRD2…)
• Indications: 12 conditions
• Clinical trials: 14
• Chemistry: 327.8 Da · C18H18ClN3O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL831
Name	Loxapine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3964
ChEBI	CHEBI:50841
ATC	N05AH01
Molecular formula	C18H18ClN3O
Molecular weight	327.8
InChIKey	XJGVXQDUIWGIRW-UHFFFAOYSA-N

SMILES: CN1CCN(CC1)C2=NC3=CC=CC=C3OC4=C2C=C(C=C4)Cl

IUPAC name: 8-chloro-6-(4-methylpiperazin-1-yl)benzo[b][1,4]benzoxazepine

Pharmacological roles (ChEBI): antipsychotic agent, dopaminergic antagonist.

Also known as: Adasuve, CL 62,362, CL-62362, Loxapina, Loxapine, SUM 3170, SUM-3170, loxapine, SID90341467, SID50103874, SID50104024, SID50104025

Parent form; salt/anhydrous children: CHEMBL1201060, CHEMBL1201155

Patent coverage: 3,654 distinct patent families (13,469 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 13,418 (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
HTR6	5-HT6 receptor	Inverse agonist	7.6	0.2%	P50406
HTR7	5-HT7 receptor	Antagonist	7.4	0.8%	P34969
DRD2	D2 receptor	Antagonist	8.3	0%	P14416
DRD3	D3 receptor	Antagonist	7.68	0%	P35462
DRD4	D4 receptor	Antagonist	8.11	0%	P21917
HRH1	H1 receptor	Antagonist	8.2	0%	P35367
KCNT1	KNa1.1	Agonist	5.36	1.2%	Q5JUK3
HTR2A	5-HT2A receptor	Inverse agonist	8.1	0%	P28223
HTR2C	5-HT2C receptor	Inverse agonist	8	0%	P28335

Broader ChEMBL bioactivity targets: 43 (assay-derived). Sample: Muscarinic acetylcholine receptor M4, 5-hydroxytryptamine receptor 2B, D(1B) dopamine receptor, Alpha-2A adrenergic receptor, 5-hydroxytryptamine receptor 3A, Adrenergic receptor alpha-1, Alpha-2C adrenergic receptor, Histamine H2 receptor, Alpha-2B adrenergic receptor, Muscarinic acetylcholine receptor M5.

Bioactivity

ChEMBL activities: 62 potent at pChembl ≥ 5 of 70 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2A	8.62	Ki	2.42	nM	CHEMBL_ACT_10878914
HTR2A	8.6	AC50	2.5	nM	CHEMBL_ACT_25173720
DRD4	8.31	Ki	4.9	nM	CHEMBL_ACT_1298557
DRD4	8.31	Ki	4.9	nM	CHEMBL_ACT_674911
P14842	8.22	IC50	6	nM	CHEMBL_ACT_351728
DRD4	8.05	Ki	9	nM	CHEMBL_ACT_10878894
HRH1	7.92	AC50	12	nM	CHEMBL_ACT_25212826
DRD4	7.85	IC50	14	nM	CHEMBL_ACT_351727
DRD4	7.84	AC50	14.4	nM	CHEMBL_ACT_25127443
HTR6	7.82	Ki	15	nM	CHEMBL_ACT_85711
HTR2B	7.75	AC50	17.8	nM	CHEMBL_ACT_25164195
P15823	7.75	IC50	18	nM	CHEMBL_ACT_351731
DRD3	7.72	AC50	19	nM	CHEMBL_ACT_25194862
DRD2	7.68	Ki	21	nM	CHEMBL_ACT_1298556
DRD2	7.68	Ki	21	nM	CHEMBL_ACT_674910
P61169	7.68	Ki	21	nM	CHEMBL_ACT_768220
DRD3	7.66	IC50	22	nM	CHEMBL_ACT_351726
DRD1	7.61	AC50	24.5	nM	CHEMBL_ACT_25115560
HTR2C	7.54	AC50	29	nM	CHEMBL_ACT_25132107
DRD3	7.5	AC50	32	nM	CHEMBL_ACT_25193837
P32305	7.37	Ki	43	nM	CHEMBL_ACT_85712
ADRA1A	7.28	AC50	52	nM	CHEMBL_ACT_25138106
DRD2	7.27	IC50	54	nM	CHEMBL_ACT_351725
HTR6	7.24	AC50	57.4	nM	CHEMBL_ACT_25118992
DRD2	7.23	AC50	58.3	nM	CHEMBL_ACT_25140649
ADRA1A	7.13	AC50	73.4	nM	CHEMBL_ACT_25219150
DRD1	6.99	AC50	102.4	nM	CHEMBL_ACT_25114811
HTR2B	6.92	AC50	120	nM	CHEMBL_ACT_25227818
HRH2	6.85	AC50	139.9	nM	CHEMBL_ACT_25114517
HTR2A	6.85	AC50	140	nM	CHEMBL_ACT_25225454

Target pathways

Aggregated over 9 target gene(s): HTR6, HTR7, DRD2, DRD3, DRD4, HRH1, KCNT1, HTR2A, HTR2C.

Top Reactome pathways

13 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
Dopamine receptors	3	DRD2, DRD3, DRD4
G alpha (q) signalling events	3	HRH1, HTR2A, HTR2C
G alpha (s) signalling events	2	HTR6, HTR7
G alpha (i) signalling events	2	DRD3, DRD4
Histamine receptors	1	HRH1
RHOBTB3 ATPase cycle	1	HTR7

Dominant GO biological processes

GO term	Targets
signal transduction	8
G protein-coupled receptor signaling pathway	8
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	6
chemical synaptic transmission	6
G protein-coupled serotonin receptor signaling pathway	5
intracellular calcium ion homeostasis	5
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	4
behavioral response to cocaine	4
adenylate cyclase-inhibiting dopamine receptor signaling pathway	3
phospholipase C-activating G protein-coupled receptor signaling pathway	3
locomotory behavior	3
visual learning	3
response to xenobiotic stimulus	3
regulation of dopamine secretion	3
response to histamine	3

Indications & clinical

Indications

12 indications (5 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
psychotic disorder	4	MONDO:0005485	EFO:0005407
bipolar disorder	4	MONDO:0004985	EFO:0009963
anxiety	3	MONDO:0011918	EFO:0005230
delirium	3	MONDO:0045057	EFO:0009267
neuralgia	2	MONDO:0021667	EFO:0005762
migraine disorder	2	MONDO:0005277	MONDO:0005277
nicotine dependence	1	MONDO:0008575	EFO:0003768
chronic obstructive pulmonary disease	1	MONDO:0005002	EFO:0000341
asthma	1	MONDO:0004979	MONDO:0004979

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

Clinical trials

Total trials: 14.

Phase distribution

Phase	Trials
Not specified	4
PHASE3	3
PHASE1	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
NCT02504450	Not specified	COMPLETED	Outcomes of Antipsychotic Medication Used in the Emergency Department
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.

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

Molecule	Source	Status	Shared targets
BREXPIPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
AMOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
CARIPRAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
CLOZAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
DOXEPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
HALOPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
IMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
KETANSERIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
MIANSERIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
NEFAZODONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
OLANZAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
PROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
QUETIAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
RISPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
THIORIDAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
THIOTHIXENE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
FANANSERIN	ChEMBL	Phase 2	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
LYSERGIDE	ChEMBL	Phase 2	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
PENFLURIDOL	ChEMBL	Phase 2	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
RITANSERIN	ChEMBL	Phase 2	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
SPIPERONE	ChEMBL	Phase 2	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
Pyrazinamide	PubChem	Approved	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6, HTR7
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR7
AMIODARONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
ASENAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
AZELASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1, HTR2A, HTR2C, HTR6, HTR7
CARVEDILOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HTR2A, HTR2C, HTR6, HTR7
CINACALCET	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1, HTR2A, HTR2C, HTR6, HTR7
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1, HTR2A, HTR2C, HTR6, HTR7
EBASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
HYDROXYZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR6, HTR7
ILOPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
IPRINDOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
KETOTIFEN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1, HTR2A, HTR2C, HTR6, HTR7
METHYSERGIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1, HTR2A, HTR2C, HTR6, HTR7
PERGOLIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
PIMOZIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
PROCHLORPERAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
PROMETHAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
SERTINDOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
SUNITINIB	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
TEGASEROD	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HTR2A, HTR2C, HTR6, HTR7
LATREPIRDINE	ChEMBL	Phase 3	DRD2, DRD3, HRH1, HTR2A, HTR2C, HTR6, HTR7
LISURIDE	ChEMBL	Phase 3	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C, HTR6
METERGOLINE	ChEMBL	Phase 2	DRD2, DRD3, HRH1, HTR2A, HTR2C, HTR6, HTR7
SPIRAMIDE	ChEMBL	Phase 2	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR6, HTR7
Fidaxomicin	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR7
Propoxyphene	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C
APOMORPHINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C
BENPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR2A, HTR2C