Benztropine

Summary

Benztropine (CHEMBL1201203) is an approved small-molecule antiparkinson drug (ATC N04AC01) targeting CHRM1, CHRM2, and SLC6A3; indicated across 4 conditions including parkinson disease and cocaine dependence.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N04AC01
• Targets: 4 (CHRM1, CHRM2, SLC6A3…)
• Indications: 4 conditions
• Clinical trials: 6
• Chemistry: 307.4 Da · C21H25NO

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1201203
Name	Benztropine
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	1201549
ChEBI	CHEBI:3048
ATC	N04AC01
Molecular formula	C21H25NO
Molecular weight	307.4
InChIKey	GIJXKZJWITVLHI-YOFSQIOKSA-N

SMILES: CN1[C@@H]2CC[C@H]1CC(C2)OC(C3=CC=CC=C3)C4=CC=CC=C4

IUPAC name: (1R,5S)-3-benzhydryloxy-8-methyl-8-azabicyclo[3.2.1]octane

ChEBI definition: Tropane in which a hydrogen at position 3 is substituted by a diphenylmethoxy group (endo-isomer). An acetylcholine receptor antagonist, it is used (particularly as its methanesulphonate salt) in the treatment of Parkinson’s disease, and to reduce parkinsonism and akathisia side effects of antipsychotic treatments.

Pharmacological roles (ChEBI): antiparkinson drug, parasympatholytic, antidyskinesia agent, muscarinic antagonist, oneirogen.

Also known as: Benzatropina, Benzatropine, Benztropine, Cobrentin, NK-02, SID29215426, benztropine, SID144204856, SID144205248, BENZTROPINE, Benztropine mesylate, benzatropine

Parent form; salt/anhydrous children: CHEMBL1200383

Patent coverage: 2,651 distinct patent families (9,334 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
CHRM1	M1 receptor	Antagonist	9.02	0.2%	P11229
CHRM2	M2 receptor	Antagonist	8.59	0%	P08172
SLC6A3	DAT	Inhibition	6.93	0.2%	Q01959
SLC6A19	B0AT1	Inhibition	4.36	0.3%	Q695T7

Broader ChEMBL bioactivity targets: 34 (assay-derived). Sample: Muscarinic acetylcholine receptor M4, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Histamine H2 receptor, Alpha-2B adrenergic receptor, Equilibrative nucleoside transporter 1, Muscarinic acetylcholine receptor M5, D(1A) dopamine receptor, Muscarinic acetylcholine receptor M2.

Bioactivity

ChEMBL activities: 85 potent at pChembl ≥ 5 of 93 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CHRM1	9.88	Ki	0.13	nM	CHEMBL_ACT_7617938
CHRM3	9.56	Ki	0.27	nM	CHEMBL_ACT_7617942
CHRM4	9.48	Ki	0.33	nM	CHEMBL_ACT_7617944
HRH1	9.43	Ki	0.37	nM	CHEMBL_ACT_7617910
CHRM1	9.26	IC50	0.54	nM	CHEMBL_ACT_7617937
P08482	9.23	Ki	0.59	nM	CHEMBL_ACT_465357
P08482	9.23	Ki	0.59	nM	CHEMBL_ACT_658596
P08482	9.02	Ki	0.95	nM	CHEMBL_ACT_625603
CHRM1	8.96	AC50	1.1	nM	CHEMBL_ACT_25210773
CHRM3	8.89	IC50	1.28	nM	CHEMBL_ACT_7617941
CHRM5	8.84	Ki	1.45	nM	CHEMBL_ACT_7617946
CHRM5	8.7	IC50	2.02	nM	CHEMBL_ACT_7617945
CHRM4	8.62	IC50	2.38	nM	CHEMBL_ACT_7617943
P10980	8.59	Ki	2.6	nM	CHEMBL_ACT_625604
HRH1	8.5	IC50	3.18	nM	CHEMBL_ACT_7617909
CHRM2	8.44	Ki	3.67	nM	CHEMBL_ACT_7617940
CHRM4	8.3	IC50	5.01	nM	CHEMBL_ACT_22447463
HTR2A	8.16	Ki	6.97	nM	CHEMBL_ACT_7619371
P23977	8.1	Ki	7.94	nM	CHEMBL_ACT_1230144
CHRM2	8	IC50	10	nM	CHEMBL_ACT_7617939
HRH1	7.88	AC50	13.3	nM	CHEMBL_ACT_25212559
CHRM3	7.7	IC50	19.95	nM	CHEMBL_ACT_22447469
HTR2A	7.62	IC50	24	nM	CHEMBL_ACT_7619370
ADRA1D	7.58	Ki	26	nM	CHEMBL_ACT_7616488
CHRM3	7.57	AC50	26.7	nM	CHEMBL_ACT_25136733
ADRA2B	7.52	Ki	30	nM	CHEMBL_ACT_7616492
HTR2C	7.5	Ki	32	nM	CHEMBL_ACT_7619375
CHRM1	7.44	AC50	36.5	nM	CHEMBL_ACT_25135500
P15823	7.39	Ki	41	nM	CHEMBL_ACT_7616486
ADRA1D	7.28	IC50	52	nM	CHEMBL_ACT_7616487

Target pathways

Aggregated over 4 target gene(s): CHRM1, CHRM2, SLC6A3, SLC6A19.

Top Reactome pathways

30 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	2	CHRM1, CHRM2
Disease	2	SLC6A19, SLC6A3
Signaling by GPCR	2	CHRM1, CHRM2
Class A/1 (Rhodopsin-like receptors)	2	CHRM1, CHRM2
Amine ligand-binding receptors	2	CHRM1, CHRM2
Transport of small molecules	2	SLC6A19, SLC6A3
GPCR downstream signalling	2	CHRM1, CHRM2
Muscarinic acetylcholine receptors	2	CHRM1, CHRM2
R-HSA-425366	2	SLC6A19, SLC6A3
SLC-mediated transmembrane transport	2	SLC6A19, SLC6A3
SLC-mediated transport of neurotransmitters	2	SLC6A19, SLC6A3
GPCR ligand binding	2	CHRM1, CHRM2
SLC transporter disorders	2	SLC6A19, SLC6A3
Disorders of transmembrane transporters	2	SLC6A19, SLC6A3
Neurotransmitter clearance	1	SLC6A3
Transmission across Chemical Synapses	1	SLC6A3
Neuronal System	1	SLC6A3
Membrane Trafficking	1	CHRM2
Amino acid transport across the plasma membrane	1	SLC6A19
Dopamine clearance from the synaptic cleft	1	SLC6A3
G alpha (q) signalling events	1	CHRM1
G alpha (i) signalling events	1	CHRM2
R-HSA-425393	1	SLC6A19
Defective transport of neurotransmitters by SLC6A19 causes Hartnup disorder (HND)	1	SLC6A19
Defective neurotransmitter clearance by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)	1	SLC6A3
Vesicle-mediated transport	1	CHRM2
Defective transport of amino acids by SLC6A19 causes Hartnup disorder (HND)	1	SLC6A19
Defective transport of neurotransmitters by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)	1	SLC6A3
Cargo recognition for clathrin-mediated endocytosis	1	CHRM2
Clathrin-mediated endocytosis	1	CHRM2

Dominant GO biological processes

GO term	Targets
signal transduction	2
G protein-coupled receptor signaling pathway	2
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	2
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway	2
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway	2
G protein-coupled acetylcholine receptor signaling pathway	2
chemical synaptic transmission	2
nervous system development	2
cognition	2
amino acid transport	2
sodium ion transmembrane transport	2
transmembrane transport	2
phospholipase C-activating G protein-coupled receptor signaling pathway	1
neuromuscular synaptic transmission	1
regulation of locomotion	1

Indications & clinical

Indications

4 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
Parkinson disease	4	MONDO:0005180	MONDO:0005180
cocaine dependence	2	MONDO:0005186	EFO:0002610
temporomandibular joint disorder	2	MONDO:0005473	EFO:0005279
sciatica	2	MONDO:0024333	HP:0011868

Clinical trials

Total trials: 6.

Phase distribution

Phase	Trials
PHASE2	4
PHASE4	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00802100	PHASE4	COMPLETED	Comparison of Optimal Antipsychotic Treatments for Adults With Schizophrenia
NCT00000333	PHASE2	COMPLETED	Evaluation of Benztropine for Cocaine Craving - 2
NCT00000793	PHASE2	COMPLETED	A Phase II/III Double-Blind Study of Amitriptyline and Mexiletine for Painful Neuropathy in HIV Infection
NCT00018200	PHASE2	COMPLETED	Effect of Antidepressants on Back Pain
NCT00066937	PHASE2	COMPLETED	Comparison of Psychological and Pharmacological Treatments for Pain Due to Temporomandibular Joint Disorder (TMD)
NCT00715377	Not specified	TERMINATED	Anticholinergic Burden in Schizophrenia

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

744 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
ACLIDINIUM BROMIDE	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
Afatinib	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
chenodiol	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
LINAGLIPTIN	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
UMECLIDINIUM	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
VORAPAXAR	ChEMBL + PubChem	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
AMIODARONE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
AMODIAQUINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
AMOXAPINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
AZELASTINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
BENPERIDOL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
BENZYDAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
BROMODIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
BROMPHENIRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CARIPRAZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CASPOFUNGIN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CINNARIZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CITALOPRAM	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CLEMASTINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CLOMIPHENE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
COBIMETINIB	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CYCLIZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CYCLOFENIL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DEQUALINIUM	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DESIPRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DESLORATADINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DEXBROMPHENIRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DEXCHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DIMENHYDRINATE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DIPHENYLPYRALINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DONEPEZIL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DOTHIEPIN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DOXAZOSIN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
DRONEDARONE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
EBASTINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
ECONAZOLE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
ELETRIPTAN	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
FLUOXETINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
HALOPERIDOL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
HEXAFLUORENIUM	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
HEXESTROL	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
HEXETIDINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
IBRUTINIB	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
ILOPERIDONE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3
IMIPRAMINE	ChEMBL	Phase 4 (approved)	CHRM1, CHRM2, SLC6A3