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Compound Detail

CHEMBL643

PROMETHAZINE
💊 Approved Drug
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💊 Approved Drug
CC(CN1c2ccccc2Sc2ccccc21)N(C)C

Basic Information

ChEMBL ID CHEMBL643
Name PROMETHAZINE
Phase Approved
Structure Type MOL
InChI Key PWWVAXIEGOYWEE-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Dimapp Diphergan Fargan NSC-30321 Proazamine Procit Prometazin Prometazina Promethazine Protazine Prothazin RP-3277 +1 more
39
Targets
79
Activities
4
Assay Types
7
PK Parameters
20
Publications
13
Known Names
16
Indications

Molecular Properties

284.4
MW (Da)
4.24
ALogP
3
HBA
0
HBD
6.5
PSA (Ų)
0.83
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1951
Availability Prescription
Chirality Racemic

Routes of Administration

Oral Parenteral Topical

Flags

Black Box Warning Natural Product

Extended Properties

Molecular Formula C17H20N2S
MW 284.43
Aromatic Rings 2
Heavy Atoms 20
NP-Likeness -0.97

Indications

Hypersensitivity Pruritus Anxiety Dementia Depressive Disorder Hyperemesis Gravidarum Migraine with Aura Migraine without Aura Nausea Pain Schizophrenia Vertigo Vomiting Crohn Disease Gastroparesis Motion Sickness

ATC Classification

D04AA10
promethazine
Level 1: DERMATOLOGICALS
Level 2: ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC.
R06AD02
promethazine
Level 1: RESPIRATORY SYSTEM
Level 2: ANTIHISTAMINES FOR SYSTEMIC USE
R06AD52
promethazine, combinations
Level 1: RESPIRATORY SYSTEM
Level 2: ANTIHISTAMINES FOR SYSTEMIC USE

Activity Summary

IC50 46 meas. best 8.54
Ki 30 meas. best 9.48
EC50 2 meas. best 6.58
Kd 1 meas. best 4.3

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Histamine H1 receptor
CHEMBL231
Ki 9.48 9.48 0.3 1
Histamine H1 receptor
CHEMBL4701
Ki 9.0 9.0 1.0 1
Muscarinic acetylcholine receptor M4
CHEMBL1821
Ki 8.98 8.98 1.1 1
Histamine H1 receptor
CHEMBL231
IC50 8.54 8.405 2.9 2
Muscarinic acetylcholine receptor M1
CHEMBL216
Ki 8.48 8.48 3.3 1
Muscarinic acetylcholine receptor M5
CHEMBL2035
Ki 8.48 8.48 3.3 1
Muscarinic acetylcholine receptor M3
CHEMBL245
Ki 8.38 8.38 4.1 1
Muscarinic acetylcholine receptor M5
CHEMBL2035
IC50 8.34 8.34 4.6 1
5-hydroxytryptamine receptor 2C
CHEMBL225
Ki 8.19 8.19 6.5 1
Muscarinic acetylcholine receptor M4
CHEMBL1821
IC50 8.12 8.12 7.6 1
5-hydroxytryptamine receptor 2C
CHEMBL225
IC50 7.92 7.92 12.0 1
Muscarinic acetylcholine receptor M2
CHEMBL211
Ki 7.92 7.92 12.0 1
Muscarinic acetylcholine receptor M1
CHEMBL216
IC50 7.85 7.85 14.0 1
5-hydroxytryptamine receptor 2A
CHEMBL224
Ki 7.72 7.72 19.0 1
Muscarinic acetylcholine receptor M3
CHEMBL245
IC50 7.7 7.7 20.0 1
Alpha-1B adrenergic receptor
CHEMBL315
Ki 7.68 7.68 21.0 1
5-hydroxytryptamine receptor 2A
CHEMBL224
IC50 7.64 7.405 23.0 2
Alpha-2B adrenergic receptor
CHEMBL1942
Ki 7.62 7.62 24.0 1
Alpha-1A adrenergic receptor
CHEMBL319
Ki 7.5 7.5 32.0 1
Muscarinic acetylcholine receptor M2
CHEMBL211
IC50 7.46 7.46 35.0 1
Alpha-1B adrenergic receptor
CHEMBL315
IC50 7.41 7.41 39.0 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
Ki 7.37 7.37 43.0 1
Alpha-2B adrenergic receptor
CHEMBL1942
IC50 7.28 7.28 53.0 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
IC50 7.17 7.17 68.0 1
Alpha-1A adrenergic receptor
CHEMBL319
IC50 7.1 7.1 79.0 1
Alpha-1D adrenergic receptor
CHEMBL223
Ki 7.05 7.05 90.0 1
D(2) dopamine receptor
CHEMBL217
IC50 7.0 6.555 100.0 2
Sigma non-opioid intracellular receptor 1
CHEMBL287
Ki 6.92 6.92 120.0 1
Alpha-1D adrenergic receptor
CHEMBL223
IC50 6.74 6.74 183.0 1
D(3) dopamine receptor
CHEMBL234
Ki 6.72 6.72 190.0 1
Alpha-2A adrenergic receptor
CHEMBL1867
Ki 6.59 6.59 256.0 1
HT-1080
CHEMBL614580
EC50 6.58 6.58 264.0 1
D(2) dopamine receptor
CHEMBL217
Ki 6.58 6.58 260.0 1
Sigma non-opioid intracellular receptor 1
CHEMBL287
IC50 6.54 6.54 287.0 1
Alpha-2C adrenergic receptor
CHEMBL1916
Ki 6.45 6.45 353.0 1
Plasmodium falciparum
CHEMBL364
IC50 6.4 5.2667 400.0 3
D(3) dopamine receptor
CHEMBL234
IC50 6.25 6.25 559.0 1
Alpha-2A adrenergic receptor
CHEMBL1867
IC50 6.17 6.17 681.0 1
Unchecked
CHEMBL612545
Ki 6.08 5.81 842.0 4
Unchecked
CHEMBL612545
IC50 6.06 5.614 866.0 5
5-hydroxytryptamine receptor 6
CHEMBL3371
Ki 5.95 5.95 1128.0 1
Histamine H2 receptor
CHEMBL1941
Ki 5.94 5.94 1146.0 1
Histamine H2 receptor
CHEMBL1941
IC50 5.93 5.93 1165.0 1
D(1A) dopamine receptor
CHEMBL2056
Ki 5.86 5.86 1372.0 1
5-hydroxytryptamine receptor 1A
CHEMBL273
Ki 5.83 5.83 1484.0 1
Sodium-dependent serotonin transporter
CHEMBL228
Ki 5.67 5.67 2130.0 1
5-hydroxytryptamine receptor 6
CHEMBL3371
IC50 5.62 5.62 2429.0 1
Alpha-2C adrenergic receptor
CHEMBL1916
IC50 5.61 5.61 2431.0 1
5-hydroxytryptamine receptor 1A
CHEMBL273
IC50 5.59 5.59 2596.0 1
D(1A) dopamine receptor
CHEMBL2056
IC50 5.56 5.56 2744.0 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 0.07 - Homo sapiens
Fu 0.09 - Homo sapiens
MRT 17.0 hr Homo sapiens
T1/2 14.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Histamine H1 receptor Ki = 0.334 nM 9.48 DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine) -
Histamine H1 receptor Ki = 1.0 nM 9.0 Displacement of [3H]pyrilamine from Sprague-Dawley rat H1 receptor assessed as i... 37951135
Muscarinic acetylcholine receptor M4 Ki = 1.057 nM 8.98 DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Histamine H1 receptor IC50 = 2.871 nM 8.54 DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine) -
Muscarinic acetylcholine receptor M5 Ki = 3.307 nM 8.48 DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor M1 Ki = 3.321 nM 8.48 DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor M3 Ki = 4.149 nM 8.38 DRUGMATRIX: Muscarinic M3 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor M5 IC50 = 4.603 nM 8.34 DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Histamine H1 receptor IC50 = 5.4 nM 8.27 Binding affinity to histamine H1 receptor (unknown origin) by radioligand bindin... 23919353
5-hydroxytryptamine receptor 2C Ki = 6.477 nM 8.19 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: ... -
Muscarinic acetylcholine receptor M4 IC50 = 7.576 nM 8.12 DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine) -
5-hydroxytryptamine receptor 2C IC50 = 12.0 nM 7.92 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: ... -
Muscarinic acetylcholine receptor M2 Ki = 12.0 nM 7.92 DRUGMATRIX: Muscarinic M2 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor M1 IC50 = 14.0 nM 7.85 DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine) -
5-hydroxytryptamine receptor 2A Ki = 19.0 nM 7.72 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: ... -
Muscarinic acetylcholine receptor M3 IC50 = 20.0 nM 7.7 DRUGMATRIX: Muscarinic M3 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Alpha-1B adrenergic receptor Ki = 21.0 nM 7.68 DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin) -
5-hydroxytryptamine receptor 2A IC50 = 23.0 nM 7.64 Binding affinity to 5HT2A receptor (unknown origin) by radioligand binding assay 23919353
Alpha-2B adrenergic receptor Ki = 24.0 nM 7.62 DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscin... -
Alpha-1A adrenergic receptor Ki = 32.0 nM 7.5 DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin) -

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885861 Rattus norvegicus 1408
- 10.6019/CHEMBL3885881 Rattus norvegicus 440
- 10.5281/zenodo.13943903 ADMET 89
31158845 10.1038/s41586-019-1291-3 ADMET 56
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
6167716 10.1021/jm00135a006 ADMET 11
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
37468498 10.1038/s41467-023-40064-9 Alpha-1A adrenergic receptor 5
24249037 10.1007/s11095-013-1232-z No relevant target 4
- 10.6019/CHEMBL4651402 SARS-CoV-2 4
18426954 10.1124/dmd.108.020479 ADMET 4
12109904 10.1021/jm011046l Plasmodium falciparum 4
37468498 10.1038/s41467-023-40064-9 D(1A) dopamine receptor 4
37468498 10.1038/s41467-023-40064-9 Muscarinic acetylcholine receptor M2 4
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 1A 4
37468498 10.1038/s41467-023-40064-9 Alpha-2A adrenergic receptor 4
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2B 4
20014752 10.1021/tx900326k Hepatotoxicity 3
12109904 10.1021/jm011046l No relevant target 3

Data from ChEMBL 36 via Core Engine