Identification

Name
Trihexyphenidyl
Accession Number
DB00376  (APRD00070)
Type
Small Molecule
Groups
Approved
Description

One of the centrally acting muscarinic antagonists used for treatment of parkinsonian disorders and drug-induced extrapyramidal movement disorders and as an antispasmodic. [PubChem]

Structure
Thumb
Synonyms
  • (RS)-1-cyclohexyl-1-phenyl-3-(1-piperidyl)propan-1-ol
  • Apo-trihex
  • Benzhexol Hydrochloride
  • Trihexifenidilo
  • Trihexyphenidyl
  • Trihexyphénidyle
  • Trihexyphenidylum
External IDs
Win 511
Product Ingredients
IngredientUNIICASInChI Key
Trihexyphenidyl HydrochlorideAO61G8257752-49-3QDWJJTJNXAKQKD-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aparkane Tab 2mgTablet2 mgOralIcn Pharmaceuticals1973-12-312005-04-26Canada
Aparkane Tab 5mgTablet5 mgOralIcn Pharmaceuticals1973-12-312005-04-26Canada
Artane Elx 2mg/5mlElixir2 mgOralLederle Cyanamid Canada Inc.1967-12-311999-08-12Canada
Artane Tab 2mgTablet2 mgOralLederle Cyanamid Canada Inc.1951-12-311999-04-12Canada
Artane Tab 5mgTablet5 mgOralLederle Cyanamid Canada Inc.1951-12-311997-01-14Canada
PMS TrihexyphenidylTablet5 mgOralPharmascience Inc1987-12-31Not applicableCanada
Trihexyphen 5 Tab 5mgTablet5 mgOralPro Doc Limitee1982-12-312010-07-13Canada
Trihexyphen Tab 2mgTablet2 mgOralPro Doc Limitee1982-12-312010-07-13Canada
TrihexyphenidylTablet2 mgOralAa Pharma Inc1982-12-31Not applicableCanada
TrihexyphenidylTablet5 mgOralAa Pharma Inc1982-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Novo-hexidyl 2mgTablet2 mgOralNovopharm Limited1968-12-312005-08-10Canada
Novo-hexidyl 5mgTablet5 mgOralNovopharm Limited1967-12-312005-08-10Canada
Nu-trihexyphenidylTablet5 mgOralNu Pharm IncNot applicableNot applicableCanada
Nu-trihexyphenidylTablet2 mgOralNu Pharm IncNot applicableNot applicableCanada
PMS-trihexyphenidylTablet2 mgOralPharmascience Inc1987-12-31Not applicableCanada
PMS-trihexyphenidyl Elx 0.4mg/mlElixir0.4 mgOralPharmascience Inc1996-10-16Not applicableCanada
Trihexyphenidyl HydrochlorideTablet5 mg/1OralState of Florida DOH Central Pharmacy2013-01-01Not applicableUs
Trihexyphenidyl HydrochlorideTablet2 mg/1OralKaiser Foundations Hospitals2017-12-18Not applicableUs
Trihexyphenidyl HydrochlorideTablet2 mg/1OralA-S Medication Solutions1987-11-012017-09-30Us
Trihexyphenidyl HydrochlorideTablet2 mg/1OralRemedy Repack2012-03-142014-01-14Us
International/Other Brands
ACA (Atlantic) / Acamed (Medifive) / Altant (Panbiotic) / Artane (Sanofi Aventis) / Artine (The Central) / Atan (Newai Chem) / Benzhexol (Johnson) / Benzox (Li Ta) / Bexol (Intas) / Broflex (Alliance) / Cyclodol (Grindeks) / Dyskinil (Crescent) / Ea Ten (Heng Hsin) / Hexymer (Mersifarma) / Hipokinon (Psicofarma) / Lahexy (La Pharmaceuticals) / Pacitane (Wyeth) / Pakisonal (Takata Seiyaku) / Parales (Psyco Remedies) / Parcisol (Milve) / Pargitan (Nevada Pharma) / Parkin (Micro Synapse) / Parkinane (Eisai) / Parkines (Towa Yakuhin) / Parkinidyl (CCPC) / Parkisan (Balkanpharma) / Parkitane (Sun) / Parkizol (Hikma) / Tonaril (Chile)
Categories
UNII
6RC5V8B7PO
CAS number
144-11-6
Weight
Average: 301.4662
Monoisotopic: 301.240564619
Chemical Formula
C20H31NO
InChI Key
HWHLPVGTWGOCJO-UHFFFAOYSA-N
InChI
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
IUPAC Name
1-cyclohexyl-1-phenyl-3-(piperidin-1-yl)propan-1-ol
SMILES
OC(CCN1CCCCC1)(C1CCCCC1)C1=CC=CC=C1

Pharmacology

Indication

Indicated for the treatment of parkinson's disease and extrapyramidal reactions caused by drugs.

Associated Conditions
Pharmacodynamics

Trihexyphenidyl 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.

Mechanism of action

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.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M1
antagonist
Human
UMuscarinic acetylcholine receptor M2
antagonist
Human
UMuscarinic acetylcholine receptor M3
antagonist
Human
UMuscarinic acetylcholine receptor M4
antagonist
Human
UMuscarinic acetylcholine receptor M5
antagonist
Human
Absorption

Trihexyphenidyl is rapidly absorbed from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

3.3-4.1 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include mydriasis, dryness of mucous membranes, red face, atonic states of bowels and bladder, and hyperthermia in high doses. Central consequences are agitation, confusion, and hallucinations. An untreated overdose may be fatal, particular in children. Premortal signs are respiratory depression and cardiac arrest.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Trihexyphenidyl can be decreased when used in combination with 1,10-Phenanthroline.
AclidiniumThe risk or severity of adverse effects can be increased when Trihexyphenidyl is combined with Aclidinium.
AgmatineThe risk or severity of adverse effects can be increased when Trihexyphenidyl is combined with Agmatine.
Ajulemic acidThe risk or severity of Tachycardia and drowsiness can be increased when Trihexyphenidyl is combined with Ajulemic acid.
AlcuroniumThe risk or severity of adverse effects can be increased when Trihexyphenidyl is combined with Alcuronium.
AlfentanilThe risk or severity of adverse effects can be increased when Trihexyphenidyl is combined with Alfentanil.
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Trihexyphenidyl is combined with Alphacetylmethadol.
AlphaprodineThe risk or severity of adverse effects can be increased when Trihexyphenidyl is combined with Alphaprodine.
Aluminum sulfateThe therapeutic efficacy of Aluminum sulfate can be decreased when used in combination with Trihexyphenidyl.
AmantadineThe risk or severity of adverse effects can be increased when Trihexyphenidyl is combined with Amantadine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014520
KEGG Compound
C07171
PubChem Compound
5572
PubChem Substance
46507717
ChemSpider
5371
BindingDB
81462
ChEBI
9720
ChEMBL
CHEMBL1490
Therapeutic Targets Database
DAP001532
PharmGKB
PA164747026
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Trihexyphenidyl
ATC Codes
N04AA01 — Trihexyphenidyl
AHFS Codes
  • 28:36.08 — Anticholinergic Agents
FDA label
Download (197 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceRosaceas1
0Not Yet RecruitingTreatmentExtrapyramidal Syndrome1
2Active Not RecruitingTreatmentMalignant Neoplasm of Stomach1
2CompletedTreatmentDystonias1
2Not Yet RecruitingTreatmentMalignant Neoplasm of Stomach1
2, 3RecruitingTreatmentMalignant Neoplasm of Stomach2
3RecruitingTreatmentMalignant Neoplasm of Stomach1
4RecruitingTreatmentMalignant Neoplasm of Stomach1
Not AvailableCompletedNot AvailableDYT 1 Dystonia / Primary Cervical Dystonia1

Pharmacoeconomics

Manufacturers
  • Lederle laboratories div american cyanamid co
  • Mikart inc
  • Pharmaceutical assoc inc div beach products
  • Pharmaceutical ventures ltd
  • Schering corp sub schering plough corp
  • Nylos trading co inc
  • Vangard laboratories inc div midway medical co
  • Vintage pharmaceuticals inc
  • Watson laboratories inc
  • West ward pharmaceutical corp
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Comprehensive Consultant Services Inc.
  • Direct Dispensing Inc.
  • Heartland Repack Services LLC
  • Kaiser Foundation Hospital
  • Mckesson Corp.
  • Mikart Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Octofoil Group Inc.
  • Pharmaceutical Association
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmacy Service Center
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Qualitest
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Richmond Pharmacy
  • Vangard Labs Inc.
  • Versapharm Inc.
  • Vintage Pharmaceuticals Inc.
  • Watson Pharmaceuticals
  • West-Ward Pharmaceuticals
Dosage forms
FormRouteStrength
ElixirOral2 mg
ElixirOral0.4 mg
TabletOral2 mg
TabletOral5 mg
SolutionOral2 mg/5mL
SyrupOral2 mg/5mL
TabletOral2 mg/1
TabletOral5 mg/1
Prices
Unit descriptionCostUnit
Trihexyphenidyl HCl 5 mg tablet0.37USD tablet
Trihexyphenidyl 5 mg tablet0.36USD tablet
Trihexyphenidyl HCl 2 mg tablet0.26USD tablet
Trihexyphenidyl 2 mg tablet0.18USD tablet
Apo-Trihex 5 mg Tablet0.07USD tablet
Apo-Trihex 2 mg Tablet0.04USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)258.5 °CNot Available
logP4.49SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.00314 mg/mLALOGPS
logP4.93ALOGPS
logP4.23ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)13.84ChemAxon
pKa (Strongest Basic)9.32ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area23.47 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity93.21 m3·mol-1ChemAxon
Polarizability36.73 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9156
Blood Brain Barrier+0.9523
Caco-2 permeable+0.6707
P-glycoprotein substrateSubstrate0.6943
P-glycoprotein inhibitor IInhibitor0.5993
P-glycoprotein inhibitor IINon-inhibitor0.7561
Renal organic cation transporterInhibitor0.7563
CYP450 2C9 substrateNon-substrate0.8256
CYP450 2D6 substrateNon-substrate0.7655
CYP450 3A4 substrateNon-substrate0.5746
CYP450 1A2 substrateNon-inhibitor0.9187
CYP450 2C9 inhibitorNon-inhibitor0.9126
CYP450 2D6 inhibitorInhibitor0.8966
CYP450 2C19 inhibitorNon-inhibitor0.9248
CYP450 3A4 inhibitorNon-inhibitor0.8506
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9543
Ames testNon AMES toxic0.8434
CarcinogenicityNon-carcinogens0.9238
BiodegradationNot ready biodegradable0.9253
Rat acute toxicity2.6751 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6676
hERG inhibition (predictor II)Inhibitor0.5713
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0002-9200000000-2092a098302f5e63b76c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-4119000000-9ed82688d3c1b39f26eb

Taxonomy

Description
This compound belongs to the class of organic compounds known as aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon atom by an aromatic hydrocarbyl group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Aralkylamines
Alternative Parents
Piperidines / Benzene and substituted derivatives / Tertiary alcohols / 1,3-aminoalcohols / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives / Aromatic alcohols
Substituents
Aralkylamine / Monocyclic benzene moiety / Piperidine / Benzenoid / 1,3-aminoalcohol / Tertiary alcohol / Tertiary amine / Tertiary aliphatic amine / Azacycle / Organoheterocyclic compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
amine (CHEBI:9720)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Prus AJ, Pehrson AL, Philibin SD, Wood JT, Vunck SA, Porter JH: The role of M1 muscarinic cholinergic receptors in the discriminative stimulus properties of N-desmethylclozapine and the atypical antipsychotic drug clozapine in rats. Psychopharmacology (Berl). 2009 Apr;203(2):295-301. doi: 10.1007/s00213-008-1262-0. Epub 2008 Aug 7. [PubMed:18685832]
  4. Giachetti A, Giraldo E, Ladinsky H, Montagna E: Binding and functional profiles of the selective M1 muscarinic receptor antagonists trihexyphenidyl and dicyclomine. Br J Pharmacol. 1986 Sep;89(1):83-90. [PubMed:2432979]
  5. Tanda G, Katz JL: Muscarinic preferential M(1) receptor antagonists enhance the discriminative-stimulus effects of cocaine in rats. Pharmacol Biochem Behav. 2007 Oct;87(4):400-4. Epub 2007 Jun 2. [PubMed:17631384]
  6. Dorje F, Wess J, Lambrecht G, Tacke R, Mutschler E, Brann MR: Antagonist binding profiles of five cloned human muscarinic receptor subtypes. J Pharmacol Exp Ther. 1991 Feb;256(2):727-33. [PubMed:1994002]
  7. Freedman SB, Beer MS, Harley EA: Muscarinic M1, M2 receptor binding. Relationship with functional efficacy. Eur J Pharmacol. 1988 Oct 26;156(1):133-42. [PubMed:3208836]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Bognar IT, Altes U, Beinhauer C, Kessler I, Fuder H: A muscarinic receptor different from the M1, M2, M3 and M4 subtypes mediates the contraction of the rabbit iris sphincter. Naunyn Schmiedebergs Arch Pharmacol. 1992 Jun;345(6):611-8. [PubMed:1635586]
  2. Dorje F, Wess J, Lambrecht G, Tacke R, Mutschler E, Brann MR: Antagonist binding profiles of five cloned human muscarinic receptor subtypes. J Pharmacol Exp Ther. 1991 Feb;256(2):727-33. [PubMed:1994002]
  3. Freedman SB, Beer MS, Harley EA: Muscarinic M1, M2 receptor binding. Relationship with functional efficacy. Eur J Pharmacol. 1988 Oct 26;156(1):133-42. [PubMed:3208836]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. Bognar IT, Altes U, Beinhauer C, Kessler I, Fuder H: A muscarinic receptor different from the M1, M2, M3 and M4 subtypes mediates the contraction of the rabbit iris sphincter. Naunyn Schmiedebergs Arch Pharmacol. 1992 Jun;345(6):611-8. [PubMed:1635586]
  2. Dorje F, Wess J, Lambrecht G, Tacke R, Mutschler E, Brann MR: Antagonist binding profiles of five cloned human muscarinic receptor subtypes. J Pharmacol Exp Ther. 1991 Feb;256(2):727-33. [PubMed:1994002]
  3. Freedman SB, Beer MS, Harley EA: Muscarinic M1, M2 receptor binding. Relationship with functional efficacy. Eur J Pharmacol. 1988 Oct 26;156(1):133-42. [PubMed:3208836]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Guanyl-nucleotide exchange factor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
Molecular Weight
53048.65 Da
References
  1. Bognar IT, Altes U, Beinhauer C, Kessler I, Fuder H: A muscarinic receptor different from the M1, M2, M3 and M4 subtypes mediates the contraction of the rabbit iris sphincter. Naunyn Schmiedebergs Arch Pharmacol. 1992 Jun;345(6):611-8. [PubMed:1635586]
  2. Dorje F, Wess J, Lambrecht G, Tacke R, Mutschler E, Brann MR: Antagonist binding profiles of five cloned human muscarinic receptor subtypes. J Pharmacol Exp Ther. 1991 Feb;256(2):727-33. [PubMed:1994002]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM5
Uniprot ID
P08912
Uniprot Name
Muscarinic acetylcholine receptor M5
Molecular Weight
60073.205 Da
References
  1. Bognar IT, Altes U, Beinhauer C, Kessler I, Fuder H: A muscarinic receptor different from the M1, M2, M3 and M4 subtypes mediates the contraction of the rabbit iris sphincter. Naunyn Schmiedebergs Arch Pharmacol. 1992 Jun;345(6):611-8. [PubMed:1635586]
  2. Dorje F, Wess J, Lambrecht G, Tacke R, Mutschler E, Brann MR: Antagonist binding profiles of five cloned human muscarinic receptor subtypes. J Pharmacol Exp Ther. 1991 Feb;256(2):727-33. [PubMed:1994002]

Drug created on June 13, 2005 07:24 / Updated on November 13, 2018 07:47