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Details

Stereochemistry RACEMIC
Molecular Formula C20H31NO
Molecular Weight 301.467
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIHEXYPHENIDYL

SMILES

c1ccc(cc1)C(CCN2CCCCC2)(C3CCCCC3)O

InChI

InChIKey=HWHLPVGTWGOCJO-UHFFFAOYSA-N
InChI=1S/C20H31NO/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

HIDE SMILES / InChI

Molecular Formula C20H31NO
Molecular Weight 301.467
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

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

-6.5136958E11
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

-6.5136958E11
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
Phenothiazines in early labour.
1967 Feb 11
Toxic psychosis induced by benzhexol hydrochloride.
1970 Oct 10
Benzhexol-induced hallucinosis.
1971 Mar 6
Benzhexol and side effects with long-acting fluphenazine therapy.
1972 Jan 29
Benzhexol-induced blindness in Parkinson's disease.
1972 Mar 4
An unusual response to chlorpromazine therapy.
1972 Oct
Depot phenothiazine treatment in acute psychosis: a sequential comparative clinical study.
1973 Jan
Comparative trial of benzhexol, amantadine, and levodopa in the treatment of Parkinson's disease.
1974 Apr
Fluphenazine enanthate induced decompensations.
1975
[Effects of diazepam on six drug-induced locomotor hyperactivities in mice (author's transl)].
1975 Dec 31
Amodiaquine-induced involuntary movements.
1976 Jul 24
Skeletal muscle necrosis following membrane-active drugs plus serotonin.
1976 May
Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule.
1978 Oct 7
Neuroleptic malignant syndrome.
1980 Jul
Reversibility of long-term tardive dyskinesia associated with antiparkinsonian medication: a case report.
1981 Aug
Lithium-induced akathisia.
1987 Feb
Dystonic reactions with metoclopramide: is there a risk population?
1987 Jun
[Parkinson's disease associated with trihexyphenidyl (THP) induced dysphonia plicae ventricularis].
1988 Apr
Successful treatment of levodopa-induced myoclonus and levodopa withdrawal-induced neuroleptic malignant syndrome. A case report.
1988 Jun
Schizophrenic psychosis associated with benzhexol (artane) therapy.
1989 Sep
[A 75-year-old man with parkinsonism and delirium].
1994 Jan
Anti-nicotinic properties of anticholinergic antiparkinson drugs.
1998 Nov
[A case of amoxapine-induced tardive dystonia successfully treated with a low dose anti-cholinergic agent].
2000 Apr
Withdrawal-emergent rabbit syndrome during dose reduction of risperidone.
2001 Aug
Effects of selected anticholinergics on acoustic startle response in rats.
2001 Dec
Parkinsonism and elevated lactic acid with sertraline.
2005 Apr
[A case of Parkinsonian syndrome, cognitive impairment and hyperammonemia induced by divalproate sodium prescribed for bipolar disorder].
2005 Jan-Feb
[Two cases of tardive Tourette syndrome].
2006
Aripiprazole-induced acute dystonia.
2006 Jun
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
Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly.
2008 Feb
Flow injection determination of benzhexol based on its sensitizing effect on the chemiluminescent reaction of Ce(IV)-sulfite.
2010 Jul-Aug
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
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.
Substance Class Chemical
Created
by admin
on Sat Jun 26 11:31:38 UTC 2021
Edited
by admin
on Sat Jun 26 11:31:38 UTC 2021
Record UNII
6RC5V8B7PO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRIHEXYPHENIDYL
HSDB   INN   VANDF   WHO-DD  
INN  
Official Name English
TRIHEXYPHENIDYL [WHO-DD]
Common Name English
NSC-12268
Code English
APO-TRIHEX
Brand Name English
TRIHEXYPHENIDYL [VANDF]
Common Name English
TRIHEXYPHENIDYL [HSDB]
Common Name English
1-CYCLOHEXYL-1-PHENYL-3-(1-PIPERIDYL)PROPAN-1-OL
Systematic Name English
TRIHEXYPHENIDYL [INN]
Common Name English
BENZHEXOL
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C38149
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
WHO-ATC N04AA01
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
LIVERTOX 999
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
NCI_THESAURUS C29704
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
WHO-VATC QN04AA01
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
Code System Code Type Description
IUPHAR
7315
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
EVMPD
SUB11295MIG
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
LACTMED
Trihexyphenidyl
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
HSDB
3196
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
DRUG CENTRAL
2745
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
FDA UNII
6RC5V8B7PO
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
PUBCHEM
5572
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
RXCUI
10811
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY RxNorm
CAS
144-11-6
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
MESH
D014282
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
ECHA (EC/EINECS)
205-614-4
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
EPA CompTox
144-11-6
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
INN
1318
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
ChEMBL
CHEMBL1490
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
NCI_THESAURUS
C61988
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
DRUG BANK
DB00376
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
WIKIPEDIA
TRIHEXYPHENIDYL
Created by admin on Sat Jun 26 11:31:38 UTC 2021 , Edited by admin on Sat Jun 26 11:31:38 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY