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Details

Stereochemistry RACEMIC
Molecular Formula C20H31NO.ClH
Molecular Weight 337.927
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIHEXYPHENIDYL HYDROCHLORIDE

SMILES

Cl.OC(CCN1CCCCC1)(C2CCCCC2)C3=CC=CC=C3

InChI

InChIKey=QDWJJTJNXAKQKD-UHFFFAOYSA-N
InChI=1S/C20H31NO.ClH/c22-20(18-10-4-1-5-11-18,19-12-6-2-7-13-19)14-17-21-15-8-3-9-16-21;/h1,4-5,10-11,19,22H,2-3,6-9,12-17H2;1H

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/006773_s036_artane.pdf

Trihexyphenidyl (Artane, Apo-Trihex, Parkin, Pacitane), also known as benzhexol and trihex has been in clinical usage for decades.It is an anticholinergic used in the symptomatic treatment of all etiologic groups of parkinsonism and drug induced extrapyramidal reactions (except tardive dyskinesia). Trihexyphenidyl possesses both anticholinergic and antihistaminic effects, although only the former has been established as therapeutically significant in the management of parkinsonism. Trihexyphenidyl is a selective M1 muscarinic acetylcholine receptor antagonist. It is able to discriminate between the M1 (cortical or neuronal) and the peripheral muscarinic subtypes (cardiac and glandular). Trihexyphenidyl partially blocks cholinergic activity in the CNS, which is responsible for the symptoms of Parkinson's disease. It is also thought to increase the availability of dopamine, a brain chemical that is critical in the initiation and smooth control of voluntary muscle movement. Trihexyphenidyl is indicated for the treatment of parkinson's disease and extrapyramidal reactions caused by drugs.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Trihexyphenidyl hydrochloride

Approved Use

Trihexyphenidyl HCl tablets are indicated as an adjunct in the treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic, and idiopathic). It is often useful as adjuvant therapy when treating these forms of parkinsonism with levodopa. Additionally, it is indicated for the control of extrapyramidal disorders caused by central nervous system drugs such as the dibenzoxazepines, phenothiazines, thioxanthenes, and butyrophenones.

Launch Date

1949
Secondary
Trihexyphenidyl hydrochloride

Approved Use

Trihexyphenidyl HCl tablets are indicated as an adjunct in the treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic, and idiopathic). It is often useful as adjuvant therapy when treating these forms of parkinsonism with levodopa. Additionally, it is indicated for the control of extrapyramidal disorders caused by central nervous system drugs such as the dibenzoxazepines, phenothiazines, thioxanthenes, and butyrophenones.

Launch Date

1949
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
14.9 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIHEXYPHENIDYL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
24.4 ng/mL
5 mg 2 times / day multiple, oral
dose: 5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TRIHEXYPHENIDYL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
294 ng × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIHEXYPHENIDYL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
334 ng × h/mL
5 mg 2 times / day multiple, oral
dose: 5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TRIHEXYPHENIDYL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10.1 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TRIHEXYPHENIDYL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
8.67 h
5 mg 2 times / day multiple, oral
dose: 5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TRIHEXYPHENIDYL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
0.55 mg/kg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 0.55 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.55 mg/kg, 1 times / day
Sources:
unhealthy, 1-18 years
n = 101
Health Status: unhealthy
Condition: cerebral palsy with dystonia or/and sialorrhea
Age Group: 1-18 years
Sex: M+F
Population Size: 101
Sources:
Disc. AE: Constipation, Gastrointestinal disorders...
AEs leading to
discontinuation/dose reduction:
Constipation (2 patients)
Gastrointestinal disorders (4 patients)
Behaviour disorder (2 patients)
Movements involuntary (1 patient)
Drowsiness (1 patient)
Skin rash (1 patient)
Sources:
40 mg multiple, oral
Higher than recommended
Dose: 40 mg
Route: oral
Route: multiple
Dose: 40 mg
Sources:
unhealthy, 25 years
n = 1
Health Status: unhealthy
Condition: drug and alcohol dependence
Age Group: 25 years
Sex: M
Population Size: 1
Sources:
Other AEs: Dependence...
Other AEs:
Dependence (1 patient)
Sources:
5 mg 28 times / day multiple, oral
Higher than recommended
Dose: 5 mg, 28 times / day
Route: oral
Route: multiple
Dose: 5 mg, 28 times / day
Sources:
unhealthy, 35 years
n = 1
Health Status: unhealthy
Condition: schizophrenic
Age Group: 35 years
Sex: F
Population Size: 1
Sources:
Other AEs: Dependence...
Other AEs:
Dependence (1 patient)
Sources:
0.75 mg/kg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 0.75 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.75 mg/kg, 1 times / day
Sources:
unhealthy, 4-15 years
n = 26
Health Status: unhealthy
Condition: cerebral palsy
Age Group: 4-15 years
Sex: M+F
Population Size: 26
Sources:
Disc. AE: Chorea, Rash...
AEs leading to
discontinuation/dose reduction:
Chorea (1 patient)
Rash (1 patient)
Hyperactivity (1 patient)
Sources:
24 mg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 24 mg, 1 times / day
Route: oral
Route: multiple
Dose: 24 mg, 1 times / day
Co-administed with::
ethopropazine(350 mg)
Sources:
unhealthy, adult
n = 52
Health Status: unhealthy
Condition: torsion dystonia
Age Group: adult
Sex: unknown
Population Size: 52
Sources:
41 mg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 41 mg, 1 times / day
Route: oral
Route: multiple
Dose: 41 mg, 1 times / day
Sources:
unhealthy, children
n = 23
Health Status: unhealthy
Condition: torsion dystonia
Age Group: children
Sex: unknown
Population Size: 23
Sources:
8 mg 1 times / day multiple, oral (mean)
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Co-administed with::
neuroleptic
Sources:
unhealthy, mean 49.7 years
n = 22
Health Status: unhealthy
Condition: schizophrenia or mental retardation
Age Group: mean 49.7 years
Sex: M+F
Population Size: 22
Sources:
Other AEs: Extrapyramidal symptoms...
Other AEs:
Extrapyramidal symptoms (77%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Drowsiness 1 patient
Disc. AE
0.55 mg/kg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 0.55 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.55 mg/kg, 1 times / day
Sources:
unhealthy, 1-18 years
n = 101
Health Status: unhealthy
Condition: cerebral palsy with dystonia or/and sialorrhea
Age Group: 1-18 years
Sex: M+F
Population Size: 101
Sources:
Movements involuntary 1 patient
Disc. AE
0.55 mg/kg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 0.55 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.55 mg/kg, 1 times / day
Sources:
unhealthy, 1-18 years
n = 101
Health Status: unhealthy
Condition: cerebral palsy with dystonia or/and sialorrhea
Age Group: 1-18 years
Sex: M+F
Population Size: 101
Sources:
Skin rash 1 patient
Disc. AE
0.55 mg/kg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 0.55 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.55 mg/kg, 1 times / day
Sources:
unhealthy, 1-18 years
n = 101
Health Status: unhealthy
Condition: cerebral palsy with dystonia or/and sialorrhea
Age Group: 1-18 years
Sex: M+F
Population Size: 101
Sources:
Behaviour disorder 2 patients
Disc. AE
0.55 mg/kg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 0.55 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.55 mg/kg, 1 times / day
Sources:
unhealthy, 1-18 years
n = 101
Health Status: unhealthy
Condition: cerebral palsy with dystonia or/and sialorrhea
Age Group: 1-18 years
Sex: M+F
Population Size: 101
Sources:
Constipation 2 patients
Disc. AE
0.55 mg/kg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 0.55 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.55 mg/kg, 1 times / day
Sources:
unhealthy, 1-18 years
n = 101
Health Status: unhealthy
Condition: cerebral palsy with dystonia or/and sialorrhea
Age Group: 1-18 years
Sex: M+F
Population Size: 101
Sources:
Gastrointestinal disorders 4 patients
Disc. AE
0.55 mg/kg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 0.55 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.55 mg/kg, 1 times / day
Sources:
unhealthy, 1-18 years
n = 101
Health Status: unhealthy
Condition: cerebral palsy with dystonia or/and sialorrhea
Age Group: 1-18 years
Sex: M+F
Population Size: 101
Sources:
Dependence 1 patient
40 mg multiple, oral
Higher than recommended
Dose: 40 mg
Route: oral
Route: multiple
Dose: 40 mg
Sources:
unhealthy, 25 years
n = 1
Health Status: unhealthy
Condition: drug and alcohol dependence
Age Group: 25 years
Sex: M
Population Size: 1
Sources:
Dependence 1 patient
5 mg 28 times / day multiple, oral
Higher than recommended
Dose: 5 mg, 28 times / day
Route: oral
Route: multiple
Dose: 5 mg, 28 times / day
Sources:
unhealthy, 35 years
n = 1
Health Status: unhealthy
Condition: schizophrenic
Age Group: 35 years
Sex: F
Population Size: 1
Sources:
Chorea 1 patient
Disc. AE
0.75 mg/kg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 0.75 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.75 mg/kg, 1 times / day
Sources:
unhealthy, 4-15 years
n = 26
Health Status: unhealthy
Condition: cerebral palsy
Age Group: 4-15 years
Sex: M+F
Population Size: 26
Sources:
Hyperactivity 1 patient
Disc. AE
0.75 mg/kg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 0.75 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.75 mg/kg, 1 times / day
Sources:
unhealthy, 4-15 years
n = 26
Health Status: unhealthy
Condition: cerebral palsy
Age Group: 4-15 years
Sex: M+F
Population Size: 26
Sources:
Rash 1 patient
Disc. AE
0.75 mg/kg 1 times / day multiple, oral (mean)
Highest studied dose
Dose: 0.75 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 0.75 mg/kg, 1 times / day
Sources:
unhealthy, 4-15 years
n = 26
Health Status: unhealthy
Condition: cerebral palsy
Age Group: 4-15 years
Sex: M+F
Population Size: 26
Sources:
Extrapyramidal symptoms 77%
8 mg 1 times / day multiple, oral (mean)
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Co-administed with::
neuroleptic
Sources:
unhealthy, mean 49.7 years
n = 22
Health Status: unhealthy
Condition: schizophrenia or mental retardation
Age Group: mean 49.7 years
Sex: M+F
Population Size: 22
Sources:
PubMed

PubMed

TitleDatePubMed
Benzhexol and side effects with long-acting fluphenazine therapy.
1972 Jan 29
Benzhexol-induced blindness in Parkinson's disease.
1972 Mar 4
Toxic liver injuries.
1973 Aug
Neuroleptics and neurologic reactions.
1973 Mar
Amodiaquine-induced involuntary movements.
1976 Jul 24
Skeletal muscle necrosis following membrane-active drugs plus serotonin.
1976 May
Anticholinergic exacerbation of phenothiazine-induced extrapyramidal syndrome.
1976 Sep
Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule.
1978 Oct 7
Intravenous lorazepam in neuroleptic-induced catatonia.
1983 Dec
Withdrawal of trihexyphenidyl.
1985 Mar
Pharmacological modification of DDT-induced tremor and hyperthermia in rats: distributional factors.
1986
Parkinson's disease and myasthenia gravis: adverse effect of trihexyphenidyl on neuromuscular transmission.
1987 May
[A case of amoxapine-induced tardive dystonia successfully treated with a low dose anti-cholinergic agent].
2000 Apr
A systematic review for evidence of efficacy of anticholinergic drugs to treat drooling.
2003 Oct
[Two cases of tardive Tourette syndrome].
2006
Sustained improvement of motor function in hemiparkinsonian rats chronically treated with low doses of caffeine or trihexyphenidyl.
2007 Jan
Psychotic disorder in a patient with central and extrapontine myelinolysis.
2007 Jun
Decreased prepulse inhibition and increased sensitivity to muscarinic, but not dopaminergic drugs in M5 muscarinic acetylcholine receptor knockout mice.
2007 May
Sclerosing mesenteritis: an ergot-related complication of pergolide therapy in Parkinson's disease?
2008 Apr 30
Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly.
2008 Feb
Evaluation of the antibradykinetic actions of 5-HT1A agonists using the mouse pole test.
2008 Jul 1
[Effection of Qing-Xuan tablets on behavior pattern and striatal TNF-alpha of Parkinson model mice].
2009 Oct
Patents

Sample Use Guides

Usual Adult Dose for Extrapyramidal Reaction 4 to 10 mg orally each day. The total daily dose is best tolerated when administered in 2 or three equally separated doses. Usual Adult Dose for Parkinson's Disease Initial: 1 mg/day; increase by 2 mg increments at intervals of 3 to 5 days Usual dose: 6 to 10 mg/day in 3 to 4 divided doses; doses of 12 to 15 mg/day may be required Drug-induced extrapyramidal symptoms: Initial: 1 mg/day; increase as necessary to usual range of 5 to 15 mg/day in 3 to 4 divided doses Use in combination with levodopa: Usual range: 3 to 6 mg/day in divided doses
Route of Administration: Oral
In Vitro Use Guide
Trihexyphenidyl 10, 50, and 100 umol/L depressed the maximal upstroke velocity (Vmax) and the action potential amplitude (APA) of SAP in guinea pig papillary muscles.
Name Type Language
TRIHEXYPHENIDYL HYDROCHLORIDE
EP   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
Common Name English
ARTANE
Brand Name English
TRIHEXYPHENIDYL HYDROCHLORIDE [ORANGE BOOK]
Common Name English
BENZHEXOL HYDROCHLORIDE [WHO-IP]
Common Name English
PARCOPANE
Common Name English
TRIHEXYPHENIDYL HCL
Common Name English
ROMPARKIN
Common Name English
1-PIPERIDINEPROPANOL, .ALPHA.-CYCLOHEXYL-.ALPHA.-PHENYL-, HYDROCHLORIDE, (±)-
Systematic Name English
TRIHEXYPHENIDYL HYDROCHLORIDE [VANDF]
Common Name English
TRIHEXYPHENIDYL HYDROCHLORIDE [JAN]
Common Name English
TREMIN
Brand Name English
TRIHEXYPHENIDYL HYDROCHLORIDE [MART.]
Common Name English
CYCLODOL
Common Name English
Trihexyphenidyl hydrochloride [WHO-DD]
Common Name English
TRIHEXYPHENIDYL HYDROCHLORIDE [USP-RS]
Common Name English
CYCLODOLUM [WHO-IP]
Common Name English
(±)-.ALPHA.-CYCLOHEXYL-.ALPHA.-PHENYL-1-PIPERIDINEPROPANOL HYDROCHLORIDE
Systematic Name English
TRIPHEDINON
Common Name English
APARKANE
Common Name English
BENZHEXOL HYDROCHLORIDE
WHO-IP  
Common Name English
TRIHEXYPHENIDYL HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
NSC-757357
Code English
TRIHEXYPHENIDYL HYDROCHLORIDE [WHO-IP]
Common Name English
TRIHEXYPHENIDYLI HYDROCHLORIDUM [WHO-IP LATIN]
Common Name English
TRIHEXYPHENIDYL HYDROCHLORIDE [MI]
Common Name English
TRIHEXYPHENIDYL HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
SEDRINA
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C38149
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
NCI_THESAURUS C29704
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
Code System Code Type Description
ECHA (EC/EINECS)
200-142-5
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY
EVMPD
SUB04961MIG
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY
DAILYMED
AO61G82577
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY
SMS_ID
100000092344
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY
EPA CompTox
DTXSID8045802
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY
PUBCHEM
66007
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY
ChEMBL
CHEMBL1490
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY
FDA UNII
AO61G82577
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY
CAS
52-49-3
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY
NCI_THESAURUS
C47771
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
TRIHEXYPHENIDYL HYDROCHLORIDE
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY Description: A white or off-white, crystalline powder; odourless or almost odourless. Solubility: Slightly soluble in water; soluble in ethanol (~750 g/l) TS and methanol R. Category: Anticholinergic; antiparkinsonism drug. Storage: Trihexyphenidyl hydrochloride should be kept in a tightly closed container. Definition: Trihexyphenidyl hydrochloride contains not less than 98.0% and not more than 101.0% of C20H31NO,HCl, calculated with reference to the dried substance.
DRUG BANK
DBSALT000448
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY
RXCUI
1115
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY RxNorm
NSC
757357
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY
MERCK INDEX
m11134
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY Merck Index
RS_ITEM_NUM
1687006
Created by admin on Fri Dec 15 16:13:31 GMT 2023 , Edited by admin on Fri Dec 15 16:13:31 GMT 2023
PRIMARY