DrugBank: Trihexyphenidyl (DB00376)

targets (5)

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Trihexifenidilo [INN-Spanish]
Trihexylphenidyl
Trihexylphenidyle
Trihexylphenizyl
Trihexyphenidyl HCl
Trihexyphenidyle
Trihexyphenidyle [INN-French]
Trihexyphenidylum [INN-Latin]
Triphenidyl

Brand names

Apo-Trihex
Artane
Artane Sequels
Benzhexol
Benzhexolum
Parkinane Retard
PMS Trihexyphenidyl
Tremin
Trihexane
Trihexy

Brand name mixtures

Not Available

Categories

Antiparkinson Agents
Antidyskinetics
Muscarinic Antagonists

CAS number

144-11-6

Weight

Average: 301.4662
Monoisotopic: 301.240564619

Chemical Formula

C₂₀H₃₁NO

InChI Key

InChIKey=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

Plain Text

IUPAC Name

1-cyclohexyl-1-phenyl-3-(piperidin-1-yl)propan-1-ol

SMILES

OC(CCN1CCCCC1)(C1CCCCC1)C1=CC=CC=C1

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Cumenes and Derivatives
Phenylpropylamines

Substructures

Hydroxy Compounds
Benzyl Alcohols and Derivatives
Benzene and Derivatives
Cumenes and Derivatives
Aliphatic and Aryl Amines
Alcohols and Polyols
Heterocyclic compounds
Aromatic compounds
Phenylpropylamines
Piperidines

Pharmacology

Indication

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

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.

Absorption

Trihexyphenidyl is rapidly absorbed from the gastrointestinal tract.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

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

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

Form	Route	Strength
Elixir	Oral
Tablet	Oral

Prices

Unit description	Cost	Unit
Trihexyphenidyl HCl 5 mg tablet	0.37 USD	tablet
Trihexyphenidyl 5 mg tablet	0.36 USD	tablet
Trihexyphenidyl HCl 2 mg tablet	0.26 USD	tablet
Trihexyphenidyl 2 mg tablet	0.18 USD	tablet
Apo-Trihex 5 mg Tablet	0.07 USD	tablet
Apo-Trihex 2 mg Tablet	0.04 USD	tablet

Patents

Not Available

Properties

State

solid

Melting point

258.5 oC

Experimental Properties

Property	Value	Source
logP	4.5	PhysProp

Predicted Properties

Property	Value	Source
water solubility	3.14e-03 g/l	ALOGPS
logP	4.93	ALOGPS
logP	4.23	ChemAxon Molconvert
logS	-4.98	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	2	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	23.47	ChemAxon Molconvert
rotatable bond count	5	ChemAxon Molconvert
refractivity	93.21	ChemAxon Molconvert
polarizability	36.73	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Compound	C07171
PubChem Compound	5572
PubChem Substance	46507717
ChemSpider	5371
Therapeutic Targets Database	DAP001532
PharmGKB	PA451778
Drug Product Database	726265
RxList	http://www.rxlist.com/cgi/generic3/trihexyphen.htm
Drugs.com	http://www.drugs.com/cdi/trihexyphenidyl.html
Wikipedia	http://en.wikipedia.org/wiki/Trihexyphenidyl

ATC Codes

N04AA01

AHFS Codes

12:08.04

PDB Entries

Not Available

FDA label

show (196.6 KB)

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Muscarinic acetylcholine receptor M1 Pharmacological action: yes Actions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover Organism class: human UniProt ID: P11229 Gene: CHRM1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 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. Epub 2008 Aug 7. Pubmed 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 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 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 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 Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed 2. Muscarinic acetylcholine receptor M2 Pharmacological action: unknown Actions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition Organism class: human UniProt ID: P08172 Gene: CHRM2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 3. Muscarinic acetylcholine receptor M3 Pharmacological action: unknown Actions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover Organism class: human UniProt ID: P20309 Gene: CHRM3 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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 4. Muscarinic acetylcholine receptor M4 Pharmacological action: unknown Actions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase Organism class: human UniProt ID: P08173 Gene: CHRM4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 5. Muscarinic acetylcholine receptor M5 Pharmacological action: unknown Actions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover Organism class: human UniProt ID: P08912 Gene: CHRM5 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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

Targets

1. Muscarinic acetylcholine receptor M1

Pharmacological action: yes
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P11229 Link_out

Gene: CHRM1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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
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. Epub 2008 Aug 7. Pubmed
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
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
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
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
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Muscarinic acetylcholine receptor M2

Pharmacological action: unknown
Actions: antagonist

Organism class: human
UniProt ID: P08172 Link_out

Gene: CHRM2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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

3. Muscarinic acetylcholine receptor M3

Pharmacological action: unknown
Actions: antagonist

Organism class: human
UniProt ID: P20309 Link_out

Gene: CHRM3 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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

4. Muscarinic acetylcholine receptor M4

Pharmacological action: unknown
Actions: antagonist

Organism class: human
UniProt ID: P08173 Link_out

Gene: CHRM4 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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

5. Muscarinic acetylcholine receptor M5

Pharmacological action: unknown
Actions: antagonist

Organism class: human
UniProt ID: P08912 Link_out

Gene: CHRM5 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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

Comments

Drug created on June 13, 2005 07:24 / Updated on November 12, 2010 08:53

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.