Compound Detail

CHEMBL629

AMITRIPTYLINE

💊 Approved Drug

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💊 Approved Drug

CN(C)CCC=C1c2ccccc2CCc2ccccc21

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL629
Name	AMITRIPTYLINE
Phase	Approved
Structure Type	MOL
InChI Key	KRMDCWKBEZIMAB-UHFFFAOYSA-N
Therapeutic	✓ Yes

Known Names

Amitriptilina Amitriptyline Damitriptyline Flavyl Laroxyl Proheptadiene Seroten Triptanol

Targets

155

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Molecular Properties

277.4

MW (Da)

4.17

ALogP

HBA

HBD

3.2

PSA (Å²)

0.81

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	1961
Availability	Prescription
Chirality	Achiral

Routes of Administration

Oral Parenteral

Flags

Black Box Warning Natural Product

USAN Stem

-triptyline

Extended Properties

Molecular Formula	C20H23N
MW	277.41
Aromatic Rings	2
Heavy Atoms	21
NP-Likeness	-0.11

Indications

Depressive Disorder Depressive Disorder Anxiety Cystitis, Interstitial Dementia Depressive Disorder, Major Fibromyalgia Headache Migraine Disorders Neuralgia Pain Schizophrenia Sleep Initiation and Maintenance Disorders Biliary Dyskinesia Bursitis Diabetes Mellitus Digestive System Diseases Inflammatory Bowel Diseases Intervertebral Disc Displacement Lung Diseases, Interstitial

ATC Classification

N06AA09

amitriptyline

Level 1: NERVOUS SYSTEM

Level 2: PSYCHOANALEPTICS

Activity Summary

IC50 99 meas. best 10.7

Ki 47 meas. best 9.26

Kd 6 meas. best 6.0

EC50 3 meas. best 4.92

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Histamine H1 receptor CHEMBL4701	IC50	10.7	10.7	0.0	1
Alpha-1A adrenergic receptor CHEMBL319	IC50	10.7	9.275	0.0	2
Histamine H1 receptor CHEMBL231	Ki	9.26	9.105	0.6	2
Muscarinic acetylcholine receptor M4 CHEMBL1821	Ki	9.13	9.13	0.7	1
Sodium-dependent serotonin transporter CHEMBL228	Ki	9.05	8.1	0.9	6
Sodium-dependent serotonin transporter CHEMBL228	IC50	8.78	7.52	1.7	2
Muscarinic acetylcholine receptor M1 CHEMBL216	Ki	8.56	8.56	2.7	1
5-hydroxytryptamine receptor 2C CHEMBL225	Ki	8.5	8.5	3.2	1
Alpha-2B adrenergic receptor CHEMBL1942	Ki	8.43	8.43	3.7	1
5-hydroxytryptamine receptor 2A CHEMBL224	Ki	8.36	8.36	4.4	1
Histamine H1 receptor CHEMBL231	IC50	8.32	8.32	4.8	1
Muscarinic acetylcholine receptor M4 CHEMBL1821	IC50	8.28	8.28	5.3	1
Muscarinic acetylcholine receptor M3 CHEMBL245	Ki	8.27	8.27	5.4	1
Alpha-1A adrenergic receptor CHEMBL319	Ki	8.25	8.25	5.6	1
Muscarinic acetylcholine receptor M5 CHEMBL2035	Ki	8.24	8.24	5.8	1
5-hydroxytryptamine receptor 2C CHEMBL225	IC50	8.22	8.22	6.0	1
Muscarinic acetylcholine receptor M5 CHEMBL2035	IC50	8.1	8.1	8.0	1
Alpha-2B adrenergic receptor CHEMBL1942	IC50	8.09	8.09	8.1	1
Alpha-2C adrenergic receptor CHEMBL1916	Ki	8.07	8.07	8.6	1
Muscarinic acetylcholine receptor M1 CHEMBL216	IC50	7.96	7.96	11.0	1
5-hydroxytryptamine receptor 2A CHEMBL224	IC50	7.82	7.82	15.0	1
Sodium-dependent noradrenaline transporter CHEMBL222	Ki	7.66	7.07	22.0	2
Sodium-dependent noradrenaline transporter CHEMBL222	IC50	7.64	6.665	23.0	2
Muscarinic acetylcholine receptor M3 CHEMBL245	IC50	7.58	7.58	26.0	1
Muscarinic acetylcholine receptor M2 CHEMBL211	Ki	7.54	7.54	29.0	1
Unchecked CHEMBL612545	IC50	7.39	5.86	41.0	7
Alpha-1B adrenergic receptor CHEMBL315	Ki	7.38	7.38	42.0	1
Serotonin (5-HT) receptor CHEMBL2094123	IC50	7.36	7.36	44.0	1
5-hydroxytryptamine receptor 2B CHEMBL1833	Ki	7.35	7.35	45.0	1
Unchecked CHEMBL612545	Ki	7.28	6.01	53.0	7
Alpha-1D adrenergic receptor CHEMBL223	Ki	7.28	7.28	52.0	1
Alpha-2C adrenergic receptor CHEMBL1916	IC50	7.23	7.23	59.0	1
D(3) dopamine receptor CHEMBL234	Ki	7.21	6.95	62.0	2
Rattus norvegicus CHEMBL376	IC50	7.21	5.5373	61.0	11
5-hydroxytryptamine receptor 6 CHEMBL3371	Ki	7.19	7.19	65.0	1
5-hydroxytryptamine receptor 2B CHEMBL1833	IC50	7.16	7.16	70.0	1
Alpha-1B adrenergic receptor CHEMBL315	IC50	7.12	7.12	76.0	1
Muscarinic acetylcholine receptor M2 CHEMBL211	IC50	7.09	7.09	81.0	1
D(1A) dopamine receptor CHEMBL2056	Ki	7.05	6.9	89.0	2
Alpha-1D adrenergic receptor CHEMBL223	IC50	6.98	6.98	105.0	1
Alpha-2A adrenergic receptor CHEMBL1867	Ki	6.88	6.88	132.0	1
5-hydroxytryptamine receptor 6 CHEMBL3371	IC50	6.85	6.85	140.0	1
D(1B) dopamine receptor CHEMBL1850	Ki	6.77	6.77	170.0	1
D(3) dopamine receptor CHEMBL234	IC50	6.74	6.74	182.0	1
D(2) dopamine receptor CHEMBL217	Ki	6.71	6.59	196.0	2
Muscarinic acetylcholine receptor CHEMBL1907609	IC50	6.52	6.52	300.0	1
Alpha-2A adrenergic receptor CHEMBL1867	IC50	6.46	6.46	351.0	1
D(1A) dopamine receptor CHEMBL2056	IC50	6.45	6.45	355.0	1
Sigma non-opioid intracellular receptor 1 CHEMBL287	Ki	6.36	6.36	433.0	1
Plasmodium falciparum CHEMBL364	IC50	6.3	6.12	500.0	2

Pharmacokinetic Data

Parameter	Value	Units	Species
CL	6.1	mL.min-1.kg-1	Homo sapiens
CL	6.0	mL.min-1.kg-1	Homo sapiens
CL	6.1	mL.min-1.kg-1	Homo sapiens
CL	6.1	mL.min-1.kg-1	Homo sapiens
F	49.0	%	Homo sapiens
Fu	0.06	-	Homo sapiens
Fu	0.07	-	Homo sapiens
Fu	0.07	-	Homo sapiens
Fu	0.09	-	Rattus norvegicus
Fu	0.01	-	Rattus norvegicus
Fu	0.009	-	Rattus norvegicus
Fu	0.0073	-	Sus scrofa
Fu	0.0083	-	Rattus norvegicus
Fu	0.0071	-	Sus scrofa
MRT	24.0	hr	Homo sapiens
T1/2	27.5	hr	-
T1/2	17.0	hr	Homo sapiens
Vd	15.0	L.kg-1	-
Vd	310.0	L.kg-1	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Alpha-1A adrenergic receptor	IC50	=	0.02	nM	10.7	Compound was tested for its inhibitory activity against Alpha-1 adrenergic recep...	10447960
Histamine H1 receptor	IC50	=	0.02	nM	10.7	Compound tested for its inhibitory activity against Histamine H1 receptor	10447960
Histamine H1 receptor	Ki	=	0.555	nM	9.26	DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine)	-
Muscarinic acetylcholine receptor M4	Ki	=	0.739	nM	9.13	DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine)	-
Sodium-dependent serotonin transporter	Ki	=	0.882	nM	9.05	DRUGMATRIX: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand bind...	-
Histamine H1 receptor	Ki	=	1.12	nM	8.95	Displacement of [3H]pyrilamine from human histamine H1 receptor expressed in CHO...	19091563
Sodium-dependent serotonin transporter	IC50	=	1.661	nM	8.78	DRUGMATRIX: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand bind...	-
Muscarinic acetylcholine receptor M1	Ki	=	2.724	nM	8.56	DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine)	-
5-hydroxytryptamine receptor 2C	Ki	=	3.168	nM	8.5	DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: ...	-
Alpha-2B adrenergic receptor	Ki	=	3.687	nM	8.43	DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscin...	-
Sodium-dependent serotonin transporter	Ki	=	4.3	nM	8.37	Displacement of [3H]Citalopram from serotonin transporter (unknown origin)	24365159
5-hydroxytryptamine receptor 2A	Ki	=	4.374	nM	8.36	DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: ...	-
Histamine H1 receptor	IC50	=	4.782	nM	8.32	DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine)	-
Muscarinic acetylcholine receptor M4	IC50	=	5.297	nM	8.28	DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine)	-
Muscarinic acetylcholine receptor M3	Ki	=	5.436	nM	8.27	DRUGMATRIX: Muscarinic M3 radioligand binding (ligand: [3H] N-Methylscopolamine)	-
Sodium-dependent serotonin transporter	Ki	=	5.4	nM	8.27	Displacement of [3H]citalopram from human SERT expressed in HEK293 cells measure...	27309376
Alpha-1A adrenergic receptor	Ki	=	5.599	nM	8.25	DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin)	-
Muscarinic acetylcholine receptor M5	Ki	=	5.762	nM	8.24	DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine)	-
5-hydroxytryptamine receptor 2C	IC50	=	6.048	nM	8.22	DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: ...	-
Muscarinic acetylcholine receptor M5	IC50	=	8.02	nM	8.1	DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine)	-

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL3885861	Rattus norvegicus	1412
-	10.6019/CHEMBL3885881	Rattus norvegicus	492
16472241	10.2174/1570163043334794	Hepatotoxicity	18
22194678	10.1371/journal.pcbi.1002310	Hepatotoxicity	14
15646539	10.1016/s0399-8320(04)95062-2	Unchecked	11
18694955	10.1128/aac.00661-08	NON-PROTEIN TARGET	8
20070106	10.1021/jm901371v	Homo sapiens	8
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
25454499	10.1021/jm501307e	High affinity nerve growth factor receptor	6
7200144	10.1021/jm00346a003	Mus musculus	6
6167716	10.1021/jm00135a006	ADMET	6
10447960	10.1021/jm9910369	ADMET	6
37468498	10.1038/s41467-023-40064-9	Thromboxane A2 receptor	5
6602886	10.1021/jm00361a009	Rattus norvegicus	5
31944697	10.1021/acs.jmedchem.9b00739	Rattus norvegicus	5
37468498	10.1038/s41467-023-40064-9	Alpha-1A adrenergic receptor	5
37468498	10.1038/s41467-023-40064-9	Muscarinic acetylcholine receptor M2	5
18426954	10.1124/dmd.108.020479	ADMET	4

Data from ChEMBL 36 via Core Engine