Trihexyphenidyl
drug drugOn this page
Also known as Apo-trihexNSC-12268TrihexifenidiloTrihexyphenidyleSID90341555SID50105266TRIHEXYPHENIDYL HYDROCHLORIDE
Summary
Trihexyphenidyl (CHEMBL1490) is an approved small molecule (ATC N04AA01) targeting CHRM1; indicated across 2 conditions including parkinson disease and dystonic disorder.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: N04AA01
- Targets: 1 (CHRM1)
- Indications: 2 conditions
- Clinical trials: 4
- Chemistry: 301.5 Da · C20H31NO
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL1490 |
| Name | Trihexyphenidyl |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 5572 |
| ATC | N04AA01 |
| Molecular formula | C20H31NO |
| Molecular weight | 301.5 |
| InChIKey | HWHLPVGTWGOCJO-UHFFFAOYSA-N |
SMILES: C1CCC(CC1)C(CCN2CCCCC2)(C3=CC=CC=C3)O
IUPAC name: 1-cyclohexyl-1-phenyl-3-piperidin-1-ylpropan-1-ol
Also known as: Apo-trihex, NSC-12268, Trihexifenidilo, Trihexyphenidyl, Trihexyphenidyle, trihexyphenidyl, SID90341555, SID50105266, TRIHEXYPHENIDYLE, TRIHEXYPHENIDYL, TRIHEXYPHENIDYL HYDROCHLORIDE
Parent form; salt/anhydrous children: CHEMBL1092
Patent coverage: 3,454 distinct patent families (12,556 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 | 8.87 | 0.2% | P11229 |
Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: Muscarinic acetylcholine receptor M4, Muscarinic acetylcholine receptor M5, Muscarinic acetylcholine receptor M2, 5-hydroxytryptamine receptor 1A, Muscarinic acetylcholine receptor M1, Mu-type opioid receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, Muscarinic acetylcholine receptor M3, Sigma non-opioid intracellular receptor 1, Cytochrome P450 2D6.
Bioactivity
ChEMBL activities: 15 potent at pChembl ≥ 5 of 18 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| CHRM4 | 9.12 | Ki | 0.76 | nM | CHEMBL_ACT_7782836 |
| CHRM1 | 8.87 | Ki | 1.35 | nM | CHEMBL_ACT_7782830 |
| CHRM1 | 8.52 | AC50 | 3 | nM | CHEMBL_ACT_25210174 |
| CHRM3 | 8.5 | Ki | 3.15 | nM | CHEMBL_ACT_7782834 |
| CHRM4 | 8.26 | IC50 | 5.48 | nM | CHEMBL_ACT_7782835 |
| CHRM1 | 8.25 | IC50 | 5.61 | nM | CHEMBL_ACT_7782829 |
| CHRM5 | 8.06 | Ki | 8.68 | nM | CHEMBL_ACT_7782838 |
| CHRM2 | 7.92 | Ki | 12 | nM | CHEMBL_ACT_7782832 |
| CHRM5 | 7.92 | IC50 | 12 | nM | CHEMBL_ACT_7782837 |
| CHRM3 | 7.82 | IC50 | 15 | nM | CHEMBL_ACT_7782833 |
| CHRM2 | 7.8 | AC50 | 16 | nM | CHEMBL_ACT_25195689 |
| CHRM2 | 7.47 | IC50 | 34 | nM | CHEMBL_ACT_7782831 |
| SIGMAR1 | 7.35 | Ki | 45 | nM | CHEMBL_ACT_7783590 |
| SIGMAR1 | 6.97 | IC50 | 108 | nM | CHEMBL_ACT_7783589 |
| CYP2D6 | 5.61 | IC50 | 2450 | nM | CHEMBL_ACT_7782761 |
Target pathways
Aggregated over 1 target gene(s): CHRM1.
Top Reactome pathways
8 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Signal Transduction | 1 | CHRM1 |
| Signaling by GPCR | 1 | CHRM1 |
| Class A/1 (Rhodopsin-like receptors) | 1 | CHRM1 |
| Amine ligand-binding receptors | 1 | CHRM1 |
| GPCR downstream signalling | 1 | CHRM1 |
| Muscarinic acetylcholine receptors | 1 | CHRM1 |
| G alpha (q) signalling events | 1 | CHRM1 |
| GPCR ligand binding | 1 | CHRM1 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| signal transduction | 1 |
| G protein-coupled receptor signaling pathway | 1 |
| G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | 1 |
| adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway | 1 |
| phospholipase C-activating G protein-coupled receptor signaling pathway | 1 |
| phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway | 1 |
| G protein-coupled acetylcholine receptor signaling pathway | 1 |
| chemical synaptic transmission | 1 |
| neuromuscular synaptic transmission | 1 |
| nervous system development | 1 |
| regulation of locomotion | 1 |
| positive regulation of monoatomic ion transport | 1 |
| saliva secretion | 1 |
| cognition | 1 |
| regulation of postsynaptic membrane potential | 1 |
Indications & clinical
Indications
1 approved indication. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).
| Indication | Phase | MONDO | EFO |
|---|---|---|---|
| Parkinson disease | 4 | MONDO:0005180 | MONDO:0005180 |
1 disease in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.
| Disease (in trials) | Phase | MONDO | EFO |
|---|---|---|---|
| dystonic disorder | 2 | MONDO:0003441 | MONDO:0003441 |
Clinical trials
Total trials: 4.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 1 |
| PHASE2 | 1 |
| EARLY_PHASE1 | 1 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04523935 | PHASE4 | COMPLETED | Excessive Crying in Children With Cerebral Palsy and Communication Deficits |
| NCT00122044 | PHASE2 | COMPLETED | Childhood Hypertonia of Central Origin: A Trial of Anticholinergic Treatment Effects |
| NCT06554288 | PHASE1 | RECRUITING | Pharmacogenomic Contributions to Trihexyphenidyl Biotransformation and Response in Children With Dystonic Cerebral Palsy |
| NCT03430596 | EARLY_PHASE1 | COMPLETED | a Pilot Study of Pramipexole to Treat Extrapyramidal Symptoms Induced by Antipsychotics |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 1 variant annotation(s) for this drug (gene-keyed; see PharmGKB).
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.
438 molecules share ≥1 primary target. Top 100 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| GENTIAN VIOLET | ChEMBL + PubChem | Phase 4 (approved) | CHRM1 |
| LINAGLIPTIN | ChEMBL + PubChem | Phase 4 (approved) | CHRM1 |
| PIMAVANSERIN | ChEMBL + PubChem | Phase 4 (approved) | CHRM1 |
| REGORAFENIB | ChEMBL + PubChem | Phase 4 (approved) | CHRM1 |
| VORAPAXAR | ChEMBL + PubChem | Phase 4 (approved) | CHRM1 |
| ACETYLCHOLINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| ACETYLCHOLINE CHLORIDE | ChEMBL | Phase 4 (approved) | CHRM1 |
| ACLIDINIUM BROMIDE | ChEMBL | Phase 4 (approved) | CHRM1 |
| AMBENONIUM | ChEMBL | Phase 4 (approved) | CHRM1 |
| AMDINOCILLIN PIVOXIL | ChEMBL | Phase 4 (approved) | CHRM1 |
| AMIODARONE | ChEMBL | Phase 4 (approved) | CHRM1 |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| AMLODIPINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| AMODIAQUINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| AMOROLFINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| AMSACRINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| ANISOTROPINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | CHRM1 |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | CHRM1 |
| ATOMOXETINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| ATROPINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| AZATADINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| AZELASTINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| BALSALAZIDE | ChEMBL | Phase 4 (approved) | CHRM1 |
| BAZEDOXIFENE | ChEMBL | Phase 4 (approved) | CHRM1 |
| BECLOMETHASONE DIPROPIONATE | ChEMBL | Phase 4 (approved) | CHRM1 |
| BENPERIDOL | ChEMBL | Phase 4 (approved) | CHRM1 |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| BENZYDAMINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | CHRM1 |
| BETAMETHASONE PHOSPHORIC ACID | ChEMBL | Phase 4 (approved) | CHRM1 |
| BETHANECHOL | ChEMBL | Phase 4 (approved) | CHRM1 |
| BEXAROTENE | ChEMBL | Phase 4 (approved) | CHRM1 |
| BIPERIDEN | ChEMBL | Phase 4 (approved) | CHRM1 |
| BITHIONOL | ChEMBL | Phase 4 (approved) | CHRM1 |
| BROMOCRIPTINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| BROMODIPHENHYDRAMINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | CHRM1 |
| BROMPHENIRAMINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| BUDESONIDE | ChEMBL | Phase 4 (approved) | CHRM1 |
| BUTRIPTYLINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CABOZANTINIB | ChEMBL | Phase 4 (approved) | CHRM1 |
| CARBACHOL | ChEMBL | Phase 4 (approved) | CHRM1 |
| CARBAMOYLCHOLINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CARBETAPENTANE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CARIPRAZINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CASPOFUNGIN | ChEMBL | Phase 4 (approved) | CHRM1 |
| CERIVASTATIN | ChEMBL | Phase 4 (approved) | CHRM1 |
| CEVIMELINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CHLORMADINONE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CHLOROQUINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CHLORPHENIRAMINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CHLORPROTHIXENE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CICLOPIROX | ChEMBL | Phase 4 (approved) | CHRM1 |
| CINACALCET | ChEMBL | Phase 4 (approved) | CHRM1 |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CITALOPRAM | ChEMBL | Phase 4 (approved) | CHRM1 |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CLIDINIUM | ChEMBL | Phase 4 (approved) | CHRM1 |
| CLOFAZIMINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CLOMIPHENE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CLOZAPINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| COBIMETINIB | ChEMBL | Phase 4 (approved) | CHRM1 |
| CRISABOROLE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CYCLIZINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CYCLOBENZAPRINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CYCLOFENIL | ChEMBL | Phase 4 (approved) | CHRM1 |
| CYCLOPENTOLATE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CYCLOTHIAZIDE | ChEMBL | Phase 4 (approved) | CHRM1 |
| CYPROHEPTADINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| DACOMITINIB | ChEMBL | Phase 4 (approved) | CHRM1 |
| DALFAMPRIDINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| DARIFENACIN | ChEMBL | Phase 4 (approved) | CHRM1 |
| DAUNORUBICIN | ChEMBL | Phase 4 (approved) | CHRM1 |
| DELAVIRDINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| DEQUALINIUM | ChEMBL | Phase 4 (approved) | CHRM1 |
| DESIPRAMINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| DESLORATADINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| DESOXIMETASONE | ChEMBL | Phase 4 (approved) | CHRM1 |
| DEXAMETHASONE PHOSPHORIC ACID | ChEMBL | Phase 4 (approved) | CHRM1 |
| DEXBROMPHENIRAMINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| DEXCHLORPHENIRAMINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| DICYCLOMINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| DIETHYLSTILBESTROL | ChEMBL | Phase 4 (approved) | CHRM1 |
| DIMENHYDRINATE | ChEMBL | Phase 4 (approved) | CHRM1 |
| DIPHEMANIL | ChEMBL | Phase 4 (approved) | CHRM1 |
| DIPHENHYDRAMINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| DIPHENIDOL | ChEMBL | Phase 4 (approved) | CHRM1 |
| DIPHENYLPYRALINE | ChEMBL | Phase 4 (approved) | CHRM1 |
| DISULFIRAM | ChEMBL | Phase 4 (approved) | CHRM1 |
| DONEPEZIL | ChEMBL | Phase 4 (approved) | CHRM1 |
| DOTHIEPIN | ChEMBL | Phase 4 (approved) | CHRM1 |
| DOXAZOSIN | ChEMBL | Phase 4 (approved) | CHRM1 |
| DOXEPIN | ChEMBL | Phase 4 (approved) | CHRM1 |
| DOXORUBICIN | ChEMBL | Phase 4 (approved) | CHRM1 |
| DRONEDARONE | ChEMBL | Phase 4 (approved) | CHRM1 |
Related Atlas pages
- Genes: CHRM1
- Indicated for: Parkinson disease
- In clinical trials for: dystonic disorder
- Drugs: Linagliptin, Pimavanserin, Regorafenib, Vorapaxar, Acetylcholine, Aclidinium Bromide, Ambenonium, Amdinocillin Pivoxil, Amiodarone, Amitriptyline, Amlodipine, Amodiaquine, Amorolfine, Amoxapine, Amsacrine, Anisotropine, Aripiprazole, Astemizole, Atomoxetine, Atropine, Azatadine, Azelastine, Balsalazide, Bazedoxifene, Beclomethasone Dipropionate, Benperidol, Benztropine, Benzydamine, Bepridil, Betamethasone Phosphoric Acid, Bethanechol, Bexarotene, Biperiden, Bithionol, Bromocriptine, Bromodiphenhydramine, Bromperidol, Brompheniramine, Budesonide, Butriptyline, Cabozantinib, Carbachol, Carbetapentane, Cariprazine, Caspofungin, Cerivastatin, Cevimeline, Chlormadinone, Chloroquine, Chlorpheniramine, Chlorpromazine, Chlorprothixene, Ciclopirox, Cinacalcet, Cinnarizine, Citalopram, Clemastine, Clidinium, Clofazimine, Clomiphene, Clomipramine, Clotrimazole, Clozapine, Cobimetinib, Crisaborole, Cyclizine, Cyclobenzaprine, Cyclofenil, Cyclopentolate, Cyclothiazide, Cyproheptadine, Dacomitinib, Dalfampridine, Darifenacin, Daunorubicin, Delavirdine, Dequalinium, Desipramine, Desloratadine, Desoximetasone, Dexamethasone Phosphoric Acid, Dexbrompheniramine, Dicyclomine, Diethylstilbestrol, Dimenhydrinate, Diphemanil, Diphenhydramine, Diphenidol, Diphenylpyraline, Disulfiram, Donepezil, Dothiepin, Doxazosin, Doxepin, Doxorubicin, Dronedarone