mianserin Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
	1796	24219-97-4

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: mianserin hydrochloride mianserin mianserine (+/-)-Mianserin mianserine hydrochloride mianserin HCl mianserine HCl	A tetracyclic compound with antidepressant effects. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors. Molecular weight: 264.37 Formula: C18H20N2 CLOGP: 3.76 LIPINSKI: 0 HAC: 2 HDO: 0 TPSA: 6.48 ALOGS: -3.06 ROTB: 0

Drug dosage:

Dose	Unit	Route
60	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	3.40 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	5 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	6.48 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	22 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	13.75 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	21.90 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.05 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	9.60 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Jan. 1, 1976	YEAR INTRODUCED

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Toxicity to various agents	131.76	27.90	141	5250	211625	46469046
Coma	125.18	27.90	80	5311	58269	46622402
Hyponatraemia	122.68	27.90	98	5293	101234	46579437
Hepatocellular injury	104.41	27.90	56	5335	29466	46651205
Somnolence	98.53	27.90	105	5286	156416	46524255
Cholestasis	89.48	27.90	49	5342	26844	46653827
Fall	81.54	27.90	140	5251	328957	46351714
Drug interaction	74.96	27.90	104	5287	202990	46477681
Bradypnoea	73.60	27.90	23	5368	3016	46677655
Agranulocytosis	69.88	27.90	39	5352	22146	46658525
Poisoning deliberate	68.77	27.90	28	5363	7898	46672773
Bradycardia	65.32	27.90	57	5334	66241	46614430
Altered state of consciousness	62.71	27.90	37	5354	23311	46657360
Camptocormia	61.99	27.90	12	5379	207	46680464
Pleurothotonus	60.62	27.90	16	5375	1149	46679522
Miosis	59.41	27.90	24	5367	6633	46674038
Sedation complication	53.84	27.90	19	5372	3626	46677045
Brain death	50.57	27.90	17	5374	2806	46677865
Thymus disorder	50.45	27.90	10	5381	196	46680475
Blood lactic acid	49.23	27.90	9	5382	112	46680559
Housebound	49.01	27.90	10	5381	228	46680443
Acute kidney injury	48.85	27.90	93	5298	235762	46444909
Extrapyramidal disorder	44.41	27.90	23	5368	11245	46669426
Confusional state	42.00	27.90	70	5321	159822	46520849
Cutaneous lymphoma	40.01	27.90	8	5383	164	46680507
Limbic encephalitis	37.36	27.90	8	5383	232	46680439
Vertigo	36.35	27.90	37	5354	52011	46628660
Behaviour disorder	35.88	27.90	12	5379	1949	46678722
Gamma-glutamyltransferase increased	34.71	27.90	29	5362	31711	46648960
Drug abuse	33.65	27.90	39	5352	63369	46617302
Drug-device interaction	33.50	27.90	6	5385	66	46680605
Disorientation	30.92	27.90	29	5362	36889	46643782
Antipsychotic drug level above therapeutic	30.87	27.90	9	5382	932	46679739
Disturbance in attention	30.77	27.90	27	5364	31533	46649138
Suicide attempt	29.45	27.90	34	5357	55002	46625669
Persecutory delusion	29.11	27.90	11	5380	2544	46678127

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Cerebral artery thrombosis	66.90	24.95	15	3676	506	29948281
Poikiloderma	50.87	24.95	10	3681	175	29948612
Somnolence	49.19	24.95	60	3631	96703	29852084
Brain scan abnormal	48.16	24.95	12	3679	641	29948146
Reticulocytosis	45.63	24.95	10	3681	303	29948484
Initial insomnia	43.11	24.95	15	3676	2574	29946213
Agranulocytosis	40.24	24.95	28	3663	21914	29926873
Adenomatous polyposis coli	39.27	24.95	8	3683	169	29948618
Hepatocellular injury	36.50	24.95	28	3663	25443	29923344
Coma	36.38	24.95	34	3657	40415	29908372
Anti-platelet antibody positive	35.73	24.95	8	3683	268	29948519
Coombs direct test positive	35.14	24.95	8	3683	289	29948498
Haptoglobin decreased	34.70	24.95	9	3682	565	29948222
Dry mouth	34.68	24.95	26	3665	22824	29925963
Meningioma	34.57	24.95	11	3680	1432	29947355
Blood glucose fluctuation	34.57	24.95	14	3677	3647	29945140
Respiratory distress	34.13	24.95	30	3661	32942	29915845
Blood bilirubin unconjugated increased	33.11	24.95	9	3682	677	29948110
Areflexia	31.29	24.95	12	3679	2707	29946080
Lichenoid keratosis	30.55	24.95	11	3680	2083	29946704
Cholestasis	28.45	24.95	24	3667	24926	29923861
Ischaemic stroke	28.05	24.95	20	3671	16255	29932532
Confusional state	26.45	24.95	54	3637	134780	29814007
Nightmare	25.93	24.95	17	3674	12059	29936728
Poor quality sleep	25.46	24.95	14	3677	7227	29941560
Skin hypertrophy	25.01	24.95	10	3681	2519	29946268

Pharmacologic Action:

Source	Code	Description
ATC	N06AX03	NERVOUS SYSTEM PSYCHOANALEPTICS ANTIDEPRESSANTS Other antidepressants
MeSH PA	D018663	Adrenergic Agents
MeSH PA	D000317	Adrenergic alpha-Antagonists
MeSH PA	D018674	Adrenergic Antagonists
MeSH PA	D000928	Antidepressive Agents
MeSH PA	D018687	Antidepressive Agents, Second-Generation
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D018494	Histamine Agents
MeSH PA	D006633	Histamine Antagonists
MeSH PA	D006634	Histamine H1 Antagonists
MeSH PA	D018377	Neurotransmitter Agents
MeSH PA	D011619	Psychotropic Drugs
MeSH PA	D018490	Serotonin Agents
MeSH PA	D012702	Serotonin Antagonists
CHEBI has role	CHEBI:35469	thymoanaleptics
CHEBI has role	CHEBI:35640	adrenergic uptake inhibitors
CHEBI has role	CHEBI:35678	histamine agonists
CHEBI has role	CHEBI:35717	sedatives
CHEBI has role	CHEBI:37890	alpha-adrenoceptor antagonists
CHEBI has role	CHEBI:37955	h1-receptor blockers
CHEBI has role	CHEBI:48279	serotonin antagonists
CHEBI has role	CHEBI:76779	prolyl oligopeptidase (ec 3.4.21.26) inhibitor

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Major depressive disorder	indication	370143000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	8.2	Basic
pKa2	1.03	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
5-hydroxytryptamine receptor 2B	GPCR	P41595	5HT2B_HUMAN	ANTAGONIST	Ki	8.12		WOMBAT-PK	IUPHAR
5-hydroxytryptamine receptor 2A	GPCR	P28223	5HT2A_HUMAN	ANTAGONIST	Ki	8.17		WOMBAT-PK	IUPHAR
5-hydroxytryptamine receptor 2C	GPCR	P28335	5HT2C_HUMAN	ANTAGONIST	Ki	8.52		WOMBAT-PK	IUPHAR
Alpha-1D adrenergic receptor	GPCR	P25100	ADA1D_HUMAN	ANTAGONIST	Ki	7.50		IUPHAR
Alpha-1B adrenergic receptor	GPCR	P35368	ADA1B_HUMAN	ANTAGONIST	Ki	7.40		IUPHAR
Histamine H2 receptor	GPCR	P25021	HRH2_HUMAN		Ki	6.00		DRUG MATRIX
Muscarinic acetylcholine receptor M1	GPCR	P11229	ACM1_HUMAN		Ki	6.46		DRUG MATRIX
Muscarinic acetylcholine receptor M2	GPCR	P08172	ACM2_HUMAN		Ki	6.42		DRUG MATRIX
Muscarinic acetylcholine receptor M3	GPCR	P20309	ACM3_HUMAN		Ki	6.53		DRUG MATRIX
Muscarinic acetylcholine receptor M4	GPCR	P08173	ACM4_HUMAN		Ki	6.54		DRUG MATRIX
Muscarinic acetylcholine receptor M5	GPCR	P08912	ACM5_HUMAN		Ki	6.64		DRUG MATRIX
5-hydroxytryptamine receptor 3A	Ion channel	P46098	5HT3A_HUMAN		Ki	6.21		DRUG MATRIX
D(3) dopamine receptor	GPCR	P35462	DRD3_HUMAN		Ki	5.55		CHEMBL
D(2) dopamine receptor	GPCR	P14416	DRD2_HUMAN		Ki	5.66		CHEMBL
D(4) dopamine receptor	GPCR	P21917	DRD4_HUMAN		IC50	5.48		CHEMBL
Sodium channel alpha subunits; brain (Types I, II, III)	Ion channel	P35498 Q99250 Q9NY46	SCN1A_HUMAN SCN2A_HUMAN SCN3A_HUMAN		IC50	5.26		CHEMBL
Alpha-1A adrenergic receptor	GPCR	P35348	ADA1A_HUMAN		IC50	6.39		CHEMBL
5-hydroxytryptamine receptor 1F	GPCR	P30939	5HT1F_HUMAN		Ki	8.06		WOMBAT-PK
Alpha-2C adrenergic receptor	GPCR	P18825	ADA2C_HUMAN		Ki	8.42		WOMBAT-PK
5-hydroxytryptamine receptor 1D	GPCR	P28221	5HT1D_HUMAN		Ki	6.99		WOMBAT-PK
5-hydroxytryptamine receptor 1B	GPCR	P28222	5HT1B_HUMAN		Ki	7.53		WOMBAT-PK
Histamine H4 receptor	GPCR	Q9H3N8	HRH4_HUMAN		EC50	6.12		WOMBAT-PK
Histamine H1 receptor	GPCR	P35367	HRH1_HUMAN		Ki	9.25		WOMBAT-PK
Alpha-2B adrenergic receptor	GPCR	P18089	ADA2B_HUMAN		Ki	7.57		WOMBAT-PK
5-hydroxytryptamine receptor 7	GPCR	P34969	5HT7R_HUMAN		Ki	7.06		WOMBAT-PK
5-hydroxytryptamine receptor 6	GPCR	P50406	5HT6R_HUMAN		Ki	7.17		WOMBAT-PK
5-hydroxytryptamine receptor 1A	GPCR	P08908	5HT1A_HUMAN		Ki	6.13		WOMBAT-PK
Sodium-dependent noradrenaline transporter	Transporter	P23975	SC6A2_HUMAN		Kd	7.15		WOMBAT-PK
Alpha-2A adrenergic receptor	GPCR	P08913	ADA2A_HUMAN		Ki	8.32		WOMBAT-PK
D(1A) dopamine receptor	GPCR	P21728	DRD1_HUMAN		Ki	6		WOMBAT-PK
Sodium-dependent dopamine transporter	Transporter	Q01959	SC6A3_HUMAN		Ki	5.03		PDSP
Sodium-dependent serotonin transporter	Transporter	P31645	SC6A4_HUMAN		Ki	5.40		PDSP
Alpha-1B adrenergic receptor	GPCR		ADA1B_RAT		Ki	7.18		DRUG MATRIX
5-hydroxytryptamine receptor 7	GPCR		5HT7R_RAT		Ki	7.20		CHEMBL
Sodium-dependent serotonin transporter	Transporter		SC6A4_RAT		IC50	5.54		CHEMBL
Serotonin 2 (5-HT2) receptor	GPCR		5HT2A_RAT 5HT2B_RAT 5HT2C_RAT		Ki	8.96		CHEMBL
Muscarinic acetylcholine receptor M5	GPCR		ACM5_RAT		IC50	5.72		CHEMBL
Serotonin 3 receptor (5HT3)	Ion channel		5HT3A_MOUSE 5HT3B_MOUSE		Ki	6.60		CHEMBL
Alpha-1A adrenergic receptor	GPCR		ADA1A_RAT		IC50	10.15		CHEMBL
Adrenergic receptor alpha-2	GPCR		ADA2A_RAT ADA2B_RAT ADA2C_RAT		Ki	7.21		CHEMBL
Serotonin 1 (5-HT1) receptor	GPCR		5HT1A_RAT 5HT1B_RAT 5HT1D_RAT 5HT1F_RAT		Ki	6.24		CHEMBL
Alpha-1A adrenergic receptor	GPCR		ADA1A_BOVIN		Ki	7.37		CHEMBL
Cerebral cortex alpha adrenergic receptor	GPCR		ADA1A_BOVIN ADA2A_BOVIN		IC50	8.22		CHEMBL
5-hydroxytryptamine receptor 1B	GPCR		5HT1B_RAT		Ki	5.33		CHEMBL
D(1A) dopamine receptor	GPCR		DRD1_RAT		Ki	5.85		CHEMBL
Alpha-2A adrenergic receptor	GPCR		ADA2A_BOVIN		Ki	7.77		CHEMBL
D(2) dopamine receptor	GPCR		DRD2_RAT		Ki	6.08		CHEMBL
Serotonin 3 (5-HT3) receptor	Ion channel		5HT3A_RAT 5HT3B_RAT		Ki	7.15		CHEMBL
Transporter	Transporter		Q9WTR4_RAT		Ki	7.59		CHEMBL
5-hydroxytryptamine receptor 2C	GPCR		5HT2C_RAT		Ki	8.85		CHEMBL
G-protein coupled receptor	Unclassified		Q9NG02_APIME		IC50	4.14		CHEMBL
D(3) dopamine receptor	GPCR		DRD3_RAT		Ki	5.82		CHEMBL
5-hydroxytryptamine receptor 2A	GPCR		5HT2A_RAT		Ki	8.82		CHEMBL
Histamine H1 receptor	GPCR		HRH1_CAVPO		Ki	9.07		CHEMBL
5-hydroxytryptamine receptor 1B	Unclassified		5HT1B_MOUSE	ANTAGONIST	Ki	8.30		IUPHAR
5-hydroxytryptamine receptor 6	GPCR		5HT6R_RAT	ANTAGONIST	Ki	7.40		IUPHAR
5-hydroxytryptamine receptor 7	GPCR		5HT7R_MOUSE	ANTAGONIST	Ki	7		IUPHAR

External reference:

ID	Source
D01358	KEGG_DRUG
21535-47-7	SECONDARY_CAS_RN
4027429	VANDF
C0025912	UMLSCUI
CHEBI:51137	CHEBI
CHEMBL6437	ChEMBL_ID
CHEMBL544428	ChEMBL_ID
D008803	MESH_DESCRIPTOR_UI
DB06148	DRUGBANK_ID
135	IUPHAR_LIGAND_ID
2543	INN_ID
250PJI13LM	UNII
4184	PUBCHEM_CID
203127	RXNORM
18113	MMSL
004006	NDDF
004007	NDDF
387565003	SNOMEDCT_US
395795008	SNOMEDCT_US
96200003	SNOMEDCT_US

Pharmaceutical products:

None