Skip to main content
Free research Free research Free compound review with research home and workspace preview
Quick search ChEMBL 36
Compound Detail

CHEMBL1628227

DOXEPIN
💊 Approved Drug
Enter ChEMBL ID:
Free Research Context This compound will appear in recent viewed items on the research home for this browser.
Research home View demo workspace
💊 Approved Drug
CN(C)CCC=C1c2ccccc2COc2ccccc21

Basic Information

ChEMBL ID CHEMBL1628227
Name DOXEPIN
Phase Approved
Structure Type MOL
InChI Key ODQWQRRAPPTVAG-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Doxepin Doxepina Doxepine Sinepin Sinequan
27
Targets
65
Activities
2
Assay Types
9
PK Parameters
20
Publications
5
Known Names
10
Indications
1
Mechanisms

Molecular Properties

279.4
MW (Da)
3.96
ALogP
2
HBA
0
HBD
12.5
PSA (Ų)
0.84
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1969
Availability Prescription
Chirality Achiral

Routes of Administration

Oral Topical

Flags

Black Box Warning Natural Product
USAN Stem -pin
USAN Year 1964

Extended Properties

Molecular Formula C19H21NO
MW 279.38
Aromatic Rings 2
Heavy Atoms 21
NP-Likeness -0.05

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Histamine H1 receptor antagonist ANTAGONIST Histamine H1 receptor

Indications

Depressive Disorder Depressive Disorder Pruritus Anxiety Dementia Schizophrenia Urticaria Breast Neoplasms Irritable Bowel Syndrome Sleep Wake Disorders

ATC Classification

D04AX01
doxepin
Level 1: DERMATOLOGICALS
Level 2: ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC.
N06AA12
doxepin
Level 1: NERVOUS SYSTEM
Level 2: PSYCHOANALEPTICS

Activity Summary

IC50 33 meas. best 11.0
Ki 32 meas. best 10.18

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Alpha-1A adrenergic receptor
CHEMBL319
IC50 11.0 8.985 0.0 2
Histamine H1 receptor
CHEMBL231
Ki 10.18 9.8433 0.1 3
Histamine H1 receptor
CHEMBL231
IC50 9.24 9.24 0.6 1
Muscarinic acetylcholine receptor M4
CHEMBL1821
Ki 8.23 8.23 5.8 1
5-hydroxytryptamine receptor 2A
CHEMBL224
Ki 7.96 7.96 11.0 1
Muscarinic acetylcholine receptor M3
CHEMBL245
Ki 7.82 7.82 15.0 1
Muscarinic acetylcholine receptor M1
CHEMBL216
Ki 7.75 7.75 18.0 1
Muscarinic acetylcholine receptor M5
CHEMBL2035
Ki 7.72 7.72 19.0 1
Sodium-dependent serotonin transporter
CHEMBL228
Ki 7.66 7.66 22.0 1
5-hydroxytryptamine receptor 2C
CHEMBL225
Ki 7.62 7.62 24.0 1
Muscarinic acetylcholine receptor M5
CHEMBL2035
IC50 7.58 7.58 26.0 1
Sodium-dependent noradrenaline transporter
CHEMBL222
Ki 7.54 7.54 29.0 1
Sodium-dependent noradrenaline transporter
CHEMBL222
IC50 7.54 7.54 29.0 1
Alpha-2B adrenergic receptor
CHEMBL1942
Ki 7.5 7.5 32.0 1
Alpha-1B adrenergic receptor
CHEMBL315
Ki 7.48 7.48 33.0 1
5-hydroxytryptamine receptor 2A
CHEMBL224
IC50 7.42 7.42 38.0 1
Sodium-dependent serotonin transporter
CHEMBL228
IC50 7.38 7.38 42.0 1
Muscarinic acetylcholine receptor M4
CHEMBL1821
IC50 7.38 7.38 42.0 1
Alpha-1A adrenergic receptor
CHEMBL319
Ki 7.37 7.37 43.0 1
5-hydroxytryptamine receptor 2C
CHEMBL225
IC50 7.34 7.34 46.0 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
Ki 7.25 7.25 56.0 1
Alpha-1D adrenergic receptor
CHEMBL223
Ki 7.24 7.24 58.0 1
Alpha-1B adrenergic receptor
CHEMBL315
IC50 7.22 7.22 60.0 1
Unchecked
CHEMBL612545
IC50 7.19 6.092 65.0 5
Muscarinic acetylcholine receptor M3
CHEMBL245
IC50 7.16 7.16 69.0 1
Alpha-2B adrenergic receptor
CHEMBL1942
IC50 7.15 7.15 71.0 1
Muscarinic acetylcholine receptor M1
CHEMBL216
IC50 7.11 7.11 77.0 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
IC50 7.05 7.05 89.0 1
Muscarinic acetylcholine receptor M2
CHEMBL211
Ki 7.04 7.04 92.0 1
5-hydroxytryptamine receptor 6
CHEMBL3371
Ki 6.98 6.905 105.0 2
Alpha-1D adrenergic receptor
CHEMBL223
IC50 6.93 6.93 118.0 1
Alpha-2C adrenergic receptor
CHEMBL1916
Ki 6.82 6.82 150.0 1
Unchecked
CHEMBL612545
Ki 6.77 6.1983 170.0 6
Serotonin (5-HT) receptor
CHEMBL2094123
IC50 6.7 6.7 200.0 1
Muscarinic acetylcholine receptor M2
CHEMBL211
IC50 6.59 6.59 258.0 1
Sigma non-opioid intracellular receptor 1
CHEMBL287
Ki 6.58 6.58 265.0 1
5-hydroxytryptamine receptor 6
CHEMBL3371
IC50 6.5 6.5 320.0 1
D(1A) dopamine receptor
CHEMBL2056
Ki 6.46 6.46 344.0 1
D(3) dopamine receptor
CHEMBL234
Ki 6.33 6.33 473.0 1
Alpha-2A adrenergic receptor
CHEMBL1867
Ki 6.3 6.3 501.0 1
Sigma non-opioid intracellular receptor 1
CHEMBL287
IC50 6.2 6.2 631.0 1
D(1A) dopamine receptor
CHEMBL2056
IC50 6.16 6.16 688.0 1
5-hydroxytryptamine receptor 1A
CHEMBL273
Ki 6.06 6.06 868.0 1
Alpha-2C adrenergic receptor
CHEMBL1916
IC50 5.99 5.99 1029.0 1
Alpha-2A adrenergic receptor
CHEMBL1867
IC50 5.88 5.88 1335.0 1
D(3) dopamine receptor
CHEMBL234
IC50 5.86 5.86 1393.0 1
5-hydroxytryptamine receptor 1A
CHEMBL273
IC50 5.82 5.82 1519.0 1
Histamine H2 receptor
CHEMBL2882
IC50 5.8 5.8 1600.0 1
Histamine H2 receptor
CHEMBL1941
Ki 5.74 5.74 1836.0 1
Histamine H2 receptor
CHEMBL1941
IC50 5.73 5.73 1867.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 14.0 mL.min-1.kg-1 Homo sapiens
CL 14.0 mL.min-1.kg-1 Homo sapiens
F 49.0 % Homo sapiens
Fu 0.025 - Rattus norvegicus
Fu 0.2 - Homo sapiens
MRT 15.0 hr Homo sapiens
T1/2 16.5 hr -
T1/2 15.0 hr Homo sapiens
T1/2 18.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Alpha-1A adrenergic receptor IC50 = 0.01 nM 11.0 Compound was tested for its inhibitory activity against Alpha-1 adrenergic recep... 10447960
Histamine H1 receptor Ki = 0.066 nM 10.18 DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine) -
Histamine H1 receptor Ki = 0.1778 nM 9.75 Displacement of [3H]mepyramine from human histamine H1 receptor expressed in HEK... 22007643
Histamine H1 receptor Ki = 0.2512 nM 9.6 Displacement of [3H]mepyramine from human wild type N-terminal hemagglutinin-tag... 27643714
Histamine H1 receptor IC50 = 0.57 nM 9.24 DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine) -
Muscarinic acetylcholine receptor M4 Ki = 5.842 nM 8.23 DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine) -
5-hydroxytryptamine receptor 2A Ki = 11.0 nM 7.96 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: ... -
Muscarinic acetylcholine receptor M3 Ki = 15.0 nM 7.82 DRUGMATRIX: Muscarinic M3 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor M1 Ki = 18.0 nM 7.75 DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor M5 Ki = 19.0 nM 7.72 DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Sodium-dependent serotonin transporter Ki = 22.0 nM 7.66 DRUGMATRIX: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand bind... -
5-hydroxytryptamine receptor 2C Ki = 24.0 nM 7.62 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: ... -
Muscarinic acetylcholine receptor M5 IC50 = 26.0 nM 7.58 DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Sodium-dependent noradrenaline transporter Ki = 29.0 nM 7.54 DRUGMATRIX: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-5... -
Sodium-dependent noradrenaline transporter IC50 = 29.0 nM 7.54 DRUGMATRIX: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-5... -
Alpha-2B adrenergic receptor Ki = 32.0 nM 7.5 DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscin... -
Alpha-1B adrenergic receptor Ki = 33.0 nM 7.48 DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin) -
5-hydroxytryptamine receptor 2A IC50 = 38.0 nM 7.42 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: ... -
Muscarinic acetylcholine receptor M4 IC50 = 42.0 nM 7.38 DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Sodium-dependent serotonin transporter IC50 = 42.0 nM 7.38 DRUGMATRIX: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand bind... -

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885861 Rattus norvegicus 1216
- 10.6019/CHEMBL3885881 Rattus norvegicus 283
- 10.5281/zenodo.13943903 ADMET 89
31158845 10.1038/s41586-019-1291-3 ADMET 57
16472241 10.2174/1570163043334794 Hepatotoxicity 18
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
6167716 10.1021/jm00135a006 ADMET 10
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
7265119 10.1021/jm00135a018 Mus musculus 7
6716399 10.1021/jm00371a011 Mus musculus 7
37468498 10.1038/s41467-023-40064-9 Alpha-1A adrenergic receptor 6
6167716 10.1021/jm00135a006 No relevant target 5
19256501 10.1021/jm801441s No relevant target 4
18426954 10.1124/dmd.108.020479 ADMET 4
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2B 4
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 1A 4
37468498 10.1038/s41467-023-40064-9 Muscarinic acetylcholine receptor M2 4
20800486 10.1016/j.bmcl.2010.07.117 Homo sapiens 4
10447960 10.1021/jm9910369 ADMET 4

Data from ChEMBL 36 via Core Engine