Mianserin

Summary

Mianserin (CHEMBL6437) is an approved small-molecule antidepressant (ATC N06AX03) targeting HTR6, HTR7, and ADRA1A; indicated across 5 conditions including depressive disorder and anxiety.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06AX03
• Targets: 11 (HTR6, HTR7, ADRA1A…)
• Indications: 5 conditions
• Clinical trials: 3
• Chemistry: 264.4 Da · C18H20N2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL6437
Name	Mianserin
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	4184
ChEBI	CHEBI:51137
ATC	N06AX03
Molecular formula	C18H20N2
Molecular weight	264.4
InChIKey	UEQUQVLFIPOEMF-UHFFFAOYSA-N

SMILES: CN1CCN2C(C1)C3=CC=CC=C3CC4=CC=CC=C42

IUPAC name: 5-methyl-2,5-diazatetracyclo[13.4.0.02,7.08,13]nonadeca-1(19),8,10,12,15,17-hexaene

ChEBI definition: A dibenzoazepine (specifically 1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2-a]azepine) methyl-substituted on N-2. Closely related to (and now mostly superseded by) the tetracyclic antidepressant mirtazapinean, it is an atypical antidepressant used in the treatment of depression throughout Europe and elsewhere.

Pharmacological roles (ChEBI): antidepressant, histamine agonist, sedative, α-adrenergic antagonist, adrenergic uptake inhibitor, serotonergic antagonist, H1-receptor antagonist, EC 3.4.21.26 (prolyl oligopeptidase) inhibitor, geroprotector.

Also known as: J16.389I, Mianserin, Mianserina, Mianserine, Tolvon, mianserin, SID26752015, SID90341017, SID104171186, SID124880671, SID50104682, MIANSERINE

Parent form; salt/anhydrous children: CHEMBL544428

Patent coverage: 3,941 distinct patent families (14,778 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 14,708 (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	Antagonist	7.3	0.2%	P50406
HTR7	5-HT7 receptor	Antagonist	7.6	0.8%	P34969
ADRA1A	α1A-adrenoceptor	Antagonist	7.6		P35348
ADRA1B	α1B-adrenoceptor	Antagonist	7.4	0%	P35368
ADRA1D	α1D-adrenoceptor	Antagonist	7.5	0.2%	P25100
LPAR1	LPA1 receptor	Antagonist	7	1.9%	Q92633
HTR1B	5-HT1B receptor	Antagonist	8.3	0.2%	P28222
HTR2A	5-HT2A receptor	Antagonist	9.6	0%	P28223
HTR2B	5-HT2B receptor	Antagonist	8.8	0.4%	P41595
HTR2C	5-HT2C receptor	Inverse agonist	9.2	0%	P28335
SLC6A2	NET	Inhibition	7.59	0.4%	P23975

Broader ChEMBL bioactivity targets: 62 (assay-derived). Sample: Prelamin-A/C, Inositol monophosphatase 1, 4’-phosphopantetheinyl transferase ffp, Ras-related protein Rab-9A, Muscarinic acetylcholine receptor M4, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, 5-hydroxytryptamine receptor 3A, Adrenergic receptor alpha-1, Alpha-2C adrenergic receptor.

Bioactivity

ChEMBL activities: 185 potent at pChembl ≥ 5 of 193 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P43140	10.15	IC50	0.07	nM	CHEMBL_ACT_780590
HRH1	9.76	Ki	0.17	nM	CHEMBL_ACT_7751928
HTR2A	9.3	Ki	0.5	nM	CHEMBL_ACT_7754034
HTR2C	9.22	Ki	0.61	nM	CHEMBL_ACT_7754038
P31389	9.07	Ki	0.85	nM	CHEMBL_ACT_233443
P08909	8.96	Ki	1.1	nM	CHEMBL_ACT_730794
HTR2C	8.94	IC50	1.16	nM	CHEMBL_ACT_7754037
HTR2A	8.92	Ki	1.2	nM	CHEMBL_ACT_18746559
P08909	8.85	Ki	1.4	nM	CHEMBL_ACT_1034124
P08909	8.85	Ki	1.4	nM	CHEMBL_ACT_257080
P14842	8.82	Ki	1.5	nM	CHEMBL_ACT_1034123
HRH1	8.82	IC50	1.51	nM	CHEMBL_ACT_7751927
HTR2C	8.77	Ki	1.7	nM	CHEMBL_ACT_12671368
HRH1	8.77	Ki	1.7	nM	CHEMBL_ACT_1518584
HTR2C	8.76	Ki	1.74	nM	CHEMBL_ACT_12668537
HTR2A	8.75	IC50	1.76	nM	CHEMBL_ACT_7754033
HRH1	8.74	AC50	1.8	nM	CHEMBL_ACT_25212906
HTR2A	8.72	Ki	1.91	nM	CHEMBL_ACT_22472195
HTR2A	8.7	Ki	2	nM	CHEMBL_ACT_18488449
HTR2A	8.66	Ki	2.2	nM	CHEMBL_ACT_18278517
P14842	8.6	Ki	2.5	nM	CHEMBL_ACT_1185780
HTR2A	8.55	Ki	2.8	nM	CHEMBL_ACT_19098489
HTR2A	8.55	Ki	2.8	nM	CHEMBL_ACT_19248956
HTR2C	8.55	AC50	2.8	nM	CHEMBL_ACT_25132183
HTR2A	8.49	Ki	3.2	nM	CHEMBL_ACT_18530155
HRH1	8.47	IC50	3.39	nM	CHEMBL_ACT_386972
P14842	8.46	Ki	3.5	nM	CHEMBL_ACT_12472566
ADRA2C	8.42	Ki	3.8	nM	CHEMBL_ACT_1518474
HTR2C	8.42	Ki	3.8	nM	CHEMBL_ACT_750831
HTR2A	8.37	Ki	4.3	nM	CHEMBL_ACT_1518483

Target pathways

Aggregated over 11 target gene(s): HTR6, HTR7, ADRA1A, ADRA1B, ADRA1D, LPAR1, HTR1B, HTR2A, HTR2B, HTR2C, SLC6A2.

Top Reactome pathways

22 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	10	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, LPAR1
Signaling by GPCR	10	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, LPAR1
Class A/1 (Rhodopsin-like receptors)	10	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, LPAR1
GPCR downstream signalling	10	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, LPAR1
GPCR ligand binding	10	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, LPAR1
Amine ligand-binding receptors	9	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7
G alpha (q) signalling events	7	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, LPAR1
Serotonin receptors	6	HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7
Adrenoceptors	3	ADRA1A, ADRA1B, ADRA1D
G alpha (12/13) signalling events	3	ADRA1A, ADRA1B, ADRA1D
G alpha (s) signalling events	2	HTR6, HTR7
G alpha (i) signalling events	2	HTR1B, LPAR1
Disease	1	SLC6A2
Transport of small molecules	1	SLC6A2
Lysosphingolipid and LPA receptors	1	LPAR1
R-HSA-425366	1	SLC6A2
SLC-mediated transmembrane transport	1	SLC6A2
SLC-mediated transport of neurotransmitters	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
signal transduction	10
G protein-coupled receptor signaling pathway	10
chemical synaptic transmission	7
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	6
G protein-coupled serotonin receptor signaling pathway	5
phospholipase C-activating G protein-coupled receptor signaling pathway	5
positive regulation of cytosolic calcium ion concentration	5
response to xenobiotic stimulus	4
positive regulation of MAPK cascade	4
positive regulation of ERK1 and ERK2 cascade	4
phospholipase C-activating serotonin receptor signaling pathway	4
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	3
smooth muscle contraction	3
vasoconstriction	3
cell-cell signaling	3

Indications & clinical

Indications

5 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
anxiety	3	MONDO:0011918	EFO:0005230
dementia	3	MONDO:0001627	HP:0000726

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

Clinical trials

Total trials: 3.

Phase distribution

Phase	Trials
PHASE4	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05599126	PHASE4	RECRUITING	A Study of Mianserin in Combination With SSRIs in Depression With Sleep Problems
NCT02761161	PHASE4	COMPLETED	Treatment of Sleep Disturbances in Trauma-affected Refugees
NCT02374567	PHASE3	TERMINATED	Pharmacovigilance in Gerontopsychiatric Patients

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 3 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.

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

Molecule	Source	Status	Shared targets
BREXPIPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
AZELASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
CLOZAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
NEFAZODONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
RISPERIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
CARIPRAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7
HALOPERIDOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
OLANZAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7
SERTINDOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
TEGASEROD	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
AMLODIPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
AMOXAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
ASENAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
CARVEDILOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
DOXEPIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
EBASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
IMIPRAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
KETOTIFEN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7
OXYMETAZOLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6
PROMAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
QUETIAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7
SALMETEROL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR7, SLC6A2
TERFENADINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
THIORIDAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
VILAZODONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2B, HTR6, HTR7, SLC6A2
LATREPIRDINE	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7
METERGOLINE	ChEMBL	Phase 2	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
NIGULDIPINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2C, HTR6, HTR7, SLC6A2
PIZOTYLINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, HTR7, SLC6A2
RITANSERIN	ChEMBL	Phase 2	ADRA1A, ADRA1B, HTR1B, HTR2A, HTR2C, HTR6, HTR7, SLC6A2
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
Pyrazinamide	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
BENZTROPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
BUSPIRONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, HTR7
CINACALCET	ChEMBL	Phase 4 (approved)	ADRA1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
CISAPRIDE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, HTR7
CLEMASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
DOXAZOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR2A, HTR2B, HTR2C, SLC6A2
ERGOTAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C, HTR6
KETANSERIN	ChEMBL	Phase 4 (approved)	ADRA1A, HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7
LOXAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
MAPROTILINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
MEPAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
PROCHLORPERAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
PROMETHAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
RALOXIFENE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, SLC6A2
XYLOMETAZOLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR2C
YOHIMBINE	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D, HTR1B, HTR2A, HTR2B, HTR6
PENFLURIDOL	ChEMBL	Phase 2	ADRA1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7, SLC6A2
SPIPERONE	ChEMBL	Phase 2	ADRA1A, ADRA1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7