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Showing drug card for Trihexyphenidyl (DB00376)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:56
Primary Accession Number DB00376
Secondary Accession Number
  • APRD00070
Name Trihexyphenidyl
Drug Type
  • Approved
  • Small Molecule
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]
Synonyms
  1. Trihexifenidilo [INN-Spanish]
  2. Trihexylphenidyl
  3. Trihexylphenidyle
  4. Trihexylphenizyl
  5. Trihexyphenidyl HCl
  6. Trihexyphenidyle
  7. Trihexyphenidyle [INN-French]
  8. Trihexyphenidylum [INN-Latin]
  9. Triphenidyl
Brand Names
  1. Apo-Trihex
  2. Artane
  3. Artane Sequels
  4. Benzhexol
  5. Benzhexolum
  6. PMS Trihexyphenidyl
  7. Parkinane Retard
  8. Tremin
  9. Trihexane
  10. Trihexy
Brand Mixtures Not Available
Chemical IUPAC Name 1-cyclohexyl-1-phenyl-3-piperidin-1-ylpropan-1-ol
Chemical Formula C20H31NO
Chemical Structure Structure
CAS Registry Number 144-11-6
InChI Identifier InChI=1/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
InChI Key HWHLPVGTWGOCJO-UHFFFAOYAW
KEGG Drug Not Available
KEGG Compound C07171 Link Image
PubChem Compound 5572 Link Image
PubChem Substance 9380 Link Image
ChEBI ID Not Available
PharmGKB ID PA451778 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00726265 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/trihexyphen.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Trihexyphenidyl Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 301.4662
Monoisotopic Molecular Weight 301.2406
State Solid
Melting Point 258.5 oC
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 3.14e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 4.5 Source: PhysProp
Predicted LogP 4.93 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.98 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES O[C@@](CCN1CCCCC1)(C1CCCCC1)C1=CC=CC=C1
Canonical SMILES OC(CCN1CCCCC1)(C1CCCCC1)C1=CC=CC=C1
Drug Category
  • Antidyskinetics
  • Antiparkinson Agents
  • Muscarinic Antagonists
ATC Codes
AHFS Codes
  • 12:08.04
Indication Indicated for the treatment of parkinson's disease and extrapyramidal reactions caused by drugs.
Pharmacology 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.
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.
Protein Binding Not Available
Biotransformation Not Available
Half Life 3.3-4.1 hours
Dosage Forms
Form Route
Elixir Oral
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Donepezil Possible antagonism of action
Galantamine Possible antagonism of action
Haloperidol The anticholinergic increases the risk of psychosis and tardive dyskinesia
Potassium Chloride The ulcerative effects of solid oral dosage forms of KCl may be enhanced by Trihexyphenidyl, an anticholinergic. Anticholinergics slow gastric emptying, increasing the contact time between the gastrointestinal mucosa and KCl. Prolonged exposure to KCl increases the risk of gastric and intestinal irritation and ulceration. Solid oral dosage forms of KCl should be avoided; alternatives include liquid or effervescent potassium preparations.
Pramlintide The anticholinergic effects of Trihexyphenidyl may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
Rivastigmine Possible antagonism of action
Secretin The stimulatory effect of Secretin may be reduced by anticholinergics such as Trihexyphenidyl. Concomitant use of Secretin and drugs with substantial anticholinergic effects should be avoided. If combination therapy must be used, Secretin efficacy should be closely monitored.
Food Interactions Not Available
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Muscarinic acetylcholine receptor M1
Drug Target 1 [top]
Target 1 ID 103
Target 1 Name Muscarinic acetylcholine receptor M1
Target 1 Synonyms Not Available
Target 1 Gene Name CHRM1
Target 1 Protein Sequence >Muscarinic acetylcholine receptor M1 
MNTSAPPAVSPNITVLAPGKGPWQVAFIGITTGLLSLATVTGNLLVLISFKVNTELKTVN
NYFLLSLACADLIIGTFSMNLYTTYLLMGHWALGTLACDLWLALDYVASNASVMNLLLIS
FDRYFSVTRPLSYRAKRTPRRAALMIGLAWLVSFVLWAPAILFWQYLVGERTVLAGQCYI
QFLSQPIITFGTAMAAFYLPVTVMCTLYWRIYRETENRARELAALQGSETPGKGGGSSSS
SERSQPGAEGSPETPPGRCCRCCRAPRLLQAYSWKEEEEEDEGSMESLTSSEGEEPGSEV
VIKMPMVDPEAQAPTKQPPRSSPNTVKRPTKKGRDRAGKGQKPRGKEQLAKRKTFSLVKE
KKAARTLSAILLAFILTWTPYNIMVLVSTFCKDCVPETLWELGYWLCYVNSTINPMCYAL
CNKAFRDTFRLLLLCRWDKRRWRKIPKRPGSVHRTPSRQC
Target 1 Number of Residues 467
Target 1 Molecular Weight 51421
Target 1 Theoretical pI 9.67
Target 1 GO Classification
Function
amine receptor activity
muscarinic acetylcholine receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in rhodopsin-like receptor activity
Target 1 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 action of G proteins. Primary transducing effect is Pi turnover
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 25-47
  • 62-82
  • 100-121
  • 142-164
  • 187-209
  • 367-387
  • 402-421
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 34451 Link Image
Target 1 UniProtKB/Swiss-Prot ID P11229 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ACM1_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1383 bp 
ATGAACACTTCAGCCCCACCTGCTGTCAGCCCCAACATCACCGTCCTGGCACCAGGAAAG
GGTCCCTGGCAAGTGGCCTTCATTGGGATCACCACGGGCCTCCTGTCGCTAGCCACAGTG
ACAGGCAACCTGCTGGTACTCATCTCTTTCAAGGTCAACACGGAGCTCAAGACAGTCAAT
AACTACTTCCTGCTGAGCCTGGCCTGTGCTGACCTCATCATCGGTACCTTCTCCATGAAC
CTCTATACCACGTACCTGCTCATGGGCCACTGGGCTCTGGGCACGCTGGCTTGTGACCTC
TGGCTGGCCCTGGACTATGTGGCCAGCAATGCCTCCGTCATGAATCTGCTGCTCATCAGC
TTTGACCGCTACTTCTCCGTGACTCGGCCCCTGAGCTACCGTGCCAAGCGCACACCCCGC
CGGGCAGCTCTGATGATCGGCCTGGCCTGGCTGGTTTCCTTTGTGCTCTGGGCCCCAGCC
ATCCTCTTCTGGCAGTACCTGGTAGGGGAGCGGACAGTGCTAGCTGGGCAGTGCTACATC
CAGTTCCTCTCCCAGCCCATCATCACCTTTGGCACAGCCATGGCTGCCTTCTACCTCCCT
GTCACAGTCATGTGCACGCTCTACTGGCGCATCTACCGGGAGACAGAGAACCGAGCACGG
GAGCTGGCAGCCCTTCAGGGCTCCGAGACGCCAGGCAAAGGGGGTGGCAGCAGCAGCAGC
TCAGAGAGGTCTCAGCCAGGGGCTGAGGGCTCACCAGAGACTCCTCCAGGCCGCTGCTGT
CGCTGCTGCCGGGCCCCCAGGCTGCTGCAGGCCTACAGCTGGAAGGAAGAAGAGGAAGAG
GACGAAGGCTCCATGGAGTCCCTCACATCCTCAGAGGGAGAGGAGCCTGGCTCCGAAGTG
GTGATCAAGATGCCAATGGTGGACCCCGAGGCACAGGCCCCCACCAAGCAGCCCCCACGG
AGCTCCCCAAATACAGTCAAGAGGCCGACTAAGAAAGGGCGTGATCGAGCTGGCAAGGGC
CAGAAGCCCCGTGGAAAGGAGCAGCTGGCCAAGCGGAAGACCTTCTCGCTGGTCAAGGAG
AAGAAGGCGGCTCGGACCCTGAGTGCCATCCTCCTGGCCTTCATCCTCACCTGGACACCG
TACAACATCATGGTGCTGGTGTCCACCTTCTGCAAGGACTGTGTTCCCGAGACCCTGTGG
GAGCTGGGCTACTGGCTGTGCTACGTCAACAGCACCATCAACCCCATGTGCTACGCACTC
TGCAACAAAGCCTTCCGGGACACCTTTCGCCTGCTGCTGCTTTGCCGCTGGGACAAGAGA
CGCTGGCGCAAGATCCCCAAGCGCCCTGGCTCCGTGCACCGCACTCCCTCCCGCCAATGC
TGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID CHRM1 Link Image
Target 1 GenAtlas ID CHRM1 Link Image
Target 1 HGNC ID HGNC:1950 Link Image
Target 1 Chromosome Location 11
Target 1 Locus 11q13
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Arden JR, Nagata O, Shockley MS, Philip M, Lameh J, Sadee W: Mutational analysis of third cytoplasmic loop domains in G-protein coupling of the HM1 muscarinic receptor. Biochem Biophys Res Commun. 1992 Nov 16;188(3):1111-5. [PubMed Link Image]
  2. Chapman CG, Browne MJ: Isolation of the human ml (Hml) muscarinic acetylcholine receptor gene by PCR amplification. Nucleic Acids Res. 1990 Apr 25;18(8):2191. [PubMed Link Image]
  3. Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ: Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J. 1987 Dec 20;6(13):3923-9. [PubMed Link Image]
  4. Allard WJ, Sigal IS, Dixon RA: Sequence of the gene encoding the human M1 muscarinic acetylcholine receptor. Nucleic Acids Res. 1987 Dec 23;15(24):10604. [PubMed Link Image]
Target 1 Drug References
  1. 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 Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

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.