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Compound Detail

CHEMBL657

DIPHENHYDRAMINE
💊 Approved Drug
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💊 Approved Drug
CN(C)CCOC(c1ccccc1)c1ccccc1

Basic Information

ChEMBL ID CHEMBL657
Name DIPHENHYDRAMINE
Phase Approved
Structure Type MOL
InChI Key ZZVUWRFHKOJYTH-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Difenhidramina Diphenhdyra Diphenhydramine Restamin
18
Targets
43
Activities
3
Assay Types
30
PK Parameters
20
Publications
4
Known Names
20
Indications

Molecular Properties

255.4
MW (Da)
3.35
ALogP
2
HBA
0
HBD
12.5
PSA (Ų)
0.78
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1946
Availability OTC
Chirality Achiral

Routes of Administration

Oral Parenteral

Flags

Natural Product

Extended Properties

Molecular Formula C17H21NO
MW 255.36
Aromatic Rings 2
Heavy Atoms 19
NP-Likeness -0.52

Indications

Hypersensitivity Pruritus Anxiety Chronic Urticaria Cough Dementia Depressive Disorder Inflammation Kidney Diseases Lupus Erythematosus, Systemic Lupus Nephritis Migraine Disorders Multiple Myeloma Multiple Sclerosis Multiple Sclerosis, Chronic Progressive Pain Rhinitis Schizophrenia Stomatitis Stomatitis

ATC Classification

D04AA32
diphenhydramine
Level 1: DERMATOLOGICALS
Level 2: ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC.
R06AA02
diphenhydramine
Level 1: RESPIRATORY SYSTEM
Level 2: ANTIHISTAMINES FOR SYSTEMIC USE
R06AA52
diphenhydramine, combinations
Level 1: RESPIRATORY SYSTEM
Level 2: ANTIHISTAMINES FOR SYSTEMIC USE

Activity Summary

IC50 27 meas. best 9.0
Ki 15 meas. best 7.83
Kd 1 meas. best 7.93

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Histamine H1 receptor
CHEMBL3943
IC50 9.0 9.0 1.0 1
Histamine H1 receptor
CHEMBL3943
Kd 7.93 7.93 11.8 1
Histamine H1 receptor
CHEMBL231
Ki 7.83 7.765 14.8 2
Muscarinic acetylcholine receptor M4
CHEMBL1821
Ki 7.28 7.28 52.0 1
Muscarinic acetylcholine receptor M1
CHEMBL216
Ki 7.08 7.08 83.0 1
Muscarinic acetylcholine receptor M5
CHEMBL2035
Ki 6.94 6.94 116.0 1
Muscarinic acetylcholine receptor M3
CHEMBL245
Ki 6.86 6.86 137.0 1
Muscarinic acetylcholine receptor M5
CHEMBL2035
IC50 6.79 6.79 162.0 1
Histamine H1 receptor
CHEMBL231
IC50 6.77 4.9767 171.0 3
Muscarinic acetylcholine receptor M1
CHEMBL216
IC50 6.46 6.46 346.0 1
Muscarinic acetylcholine receptor M4
CHEMBL1821
IC50 6.43 6.43 372.0 1
5-hydroxytryptamine receptor 2A
CHEMBL224
Ki 6.43 6.43 370.0 1
Muscarinic acetylcholine receptor M2
CHEMBL211
Ki 6.43 6.43 373.0 1
5-hydroxytryptamine receptor 2C
CHEMBL225
Ki 6.29 6.29 513.0 1
Muscarinic acetylcholine receptor M3
CHEMBL245
IC50 6.19 6.19 647.0 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
Ki 6.15 6.15 711.0 1
5-hydroxytryptamine receptor 2C
CHEMBL225
IC50 6.01 6.01 980.0 1
Muscarinic acetylcholine receptor M2
CHEMBL211
IC50 5.98 5.98 1050.0 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
IC50 5.95 5.95 1118.0 1
5-hydroxytryptamine receptor 2A
CHEMBL224
IC50 5.89 5.89 1295.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.59 4.8467 2570.4 6
Sodium-dependent noradrenaline transporter
CHEMBL222
Ki 5.45 5.45 3513.0 1
Sodium-dependent noradrenaline transporter
CHEMBL222
IC50 5.45 5.45 3542.0 1
Sodium channel alpha subunits; brain (Types I, II, III)
CHEMBL2096682
IC50 5.22 5.22 6000.0 1
Unchecked
CHEMBL612545
Ki 5.15 5.15 7078.0 1
Unchecked
CHEMBL612545
IC50 5.14 5.14 7280.0 1
Histamine H4 receptor
CHEMBL3759
IC50 4.96 4.96 11000.0 1
Histamine H4 receptor
CHEMBL3759
Ki 4.96 4.665 11000.0 2
Solute carrier family 22 member 1
CHEMBL2073670
IC50 4.62 4.62 24000.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
Ki 4.58 4.58 26101.3 1
Solute carrier family 22 member 2
CHEMBL1770032
IC50 4.5 4.5 32000.0 1
Sodium channel protein type 5 subunit alpha
CHEMBL1980
IC50 4.39 4.39 41000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 679.6 mL.min-1.g-1 Rattus norvegicus
CL 679.6 mL.min-1.g-1 Rattus norvegicus
CL 9.8 mL.min-1.kg-1 Homo sapiens
CL 9.8 mL.min-1.kg-1 Homo sapiens
CL 680.0 uL/min Rattus norvegicus
CL 53.0 mL.min-1.kg-1 Rattus norvegicus
CL 49.68 mL.min-1.g-1 Mus musculus
F 79.0 % Homo sapiens
F 72.0 % Homo sapiens
Fu 0.22 - -
Fu 0.019 - -
Fu 0.22 - Homo sapiens
Fu 0.19 - Homo sapiens
Fu 0.48 - Rattus norvegicus
Fu 0.093 - Rattus norvegicus
Fu 0.042 - Homo sapiens
Fu 0.047 - Macaca fascicularis
Fu 0.04 - Canis lupus familiaris
Fu 0.038 - Cavia porcellus
Fu 0.054 - Mus musculus
Fu 0.027 - Rattus norvegicus
Fu 0.027 - Rattus norvegicus
MRT 11.0 hr Homo sapiens
T1/2 31.05 hr Homo sapiens
T1/2 0.1133 hr Rattus norvegicus
T1/2 0.1133 hr Rattus norvegicus
T1/2 9.3 hr Homo sapiens
T1/2 0.1167 hr Rattus norvegicus
T1/2 0.5 hr Mus musculus
T1/2 0.2833 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Histamine H1 receptor IC50 = 1.0 nM 9.0 Antihistaminic activity against Histamine H1 receptor was measured on isolated t... 1977909
Histamine H1 receptor Kd = 11.75 nM 7.93 Antagonist activity at H1R in guinea pig ileum assessed as inhibition of histami... 21944853
Histamine H1 receptor Ki = 14.79 nM 7.83 Displacement of [3H]mepyramine from human H1R expressed in Sf9 cells co-expressi... 21944853
Histamine H1 receptor Ki = 20.0 nM 7.7 DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine) -
Muscarinic acetylcholine receptor M4 Ki = 52.0 nM 7.28 DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor M1 Ki = 83.0 nM 7.08 DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor M5 Ki = 116.0 nM 6.94 DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor M3 Ki = 137.0 nM 6.86 DRUGMATRIX: Muscarinic M3 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor M5 IC50 = 162.0 nM 6.79 DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Histamine H1 receptor IC50 = 171.0 nM 6.77 DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine) -
Muscarinic acetylcholine receptor M1 IC50 = 346.0 nM 6.46 DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine) -
Muscarinic acetylcholine receptor M2 Ki = 373.0 nM 6.43 DRUGMATRIX: Muscarinic M2 radioligand binding (ligand: [3H] N-Methylscopolamine) -
5-hydroxytryptamine receptor 2A Ki = 370.0 nM 6.43 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: ... -
Muscarinic acetylcholine receptor M4 IC50 = 372.0 nM 6.43 DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine) -
5-hydroxytryptamine receptor 2C Ki = 513.0 nM 6.29 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: ... -
Muscarinic acetylcholine receptor M3 IC50 = 647.0 nM 6.19 DRUGMATRIX: Muscarinic M3 radioligand binding (ligand: [3H] N-Methylscopolamine) -
5-hydroxytryptamine receptor 2B Ki = 711.0 nM 6.15 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: ... -
5-hydroxytryptamine receptor 2C IC50 = 980.0 nM 6.01 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: ... -
Muscarinic acetylcholine receptor M2 IC50 = 1050.0 nM 5.98 DRUGMATRIX: Muscarinic M2 radioligand binding (ligand: [3H] N-Methylscopolamine) -
5-hydroxytryptamine receptor 2B IC50 = 1118.0 nM 5.95 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: ... -

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885881 Rattus norvegicus 467
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
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 6
21474681 10.1124/dmd.111.038778 Brain 5
12061889 10.1021/jm0200409 ADMET 5
37468498 10.1038/s41467-023-40064-9 Muscarinic acetylcholine receptor M2 4
37468498 10.1038/s41467-023-40064-9 Alpha-2A adrenergic receptor 4
37468498 10.1038/s41467-023-40064-9 Cannabinoid receptor 1 4
2570152 10.1021/jm00129a026 Cavia porcellus 4
18426954 10.1124/dmd.108.020479 ADMET 4
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 1A 4
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 2B 4
37468498 10.1038/s41467-023-40064-9 Mu-type opioid receptor 3
19764786 10.1021/jm901036q Plasma 3
37468498 10.1038/s41467-023-40064-9 D(1A) dopamine receptor 3
21149540 10.1124/dmd.110.035998 Brain 3
7913134 10.1021/jm00039a010 Mus musculus 3
37468498 10.1038/s41467-023-40064-9 Thromboxane A2 receptor 3

Data from ChEMBL 36 via Core Engine