Tmic
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Record Information
Version2.0
Creation Date2009-07-21 20:26:45 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2770
Identification
Common NameTrihexyphenidyl
ClassSmall Molecule
DescriptionTrihexyphenidyl is only found in individuals that have used or taken this drug. It is one of the centrally acting muscarinic antagonists used for treatment of parkinsonian disorders and drug-induced extrapyramidal movement disorders and as an antispasmodic. 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.
Compound Type
  • Amine
  • Antidyskinetic
  • Antiparkinson Agent
  • Drug
  • Metabolite
  • Muscarinic Antagonist
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(RS)-1-cyclohexyl-1-phenyl-3-(1-piperidyl)propan-1-ol
ACA
Acamed
Altant
Apo-trihex
Artane
Artine
Atan
Benzhexol
Benzhexol Hydrochloride
Benzox
Bexol
Broflex
Cyclodol
Dyskinil
Ea Ten
Hexymer
Hipokinon
Lahexy
Pacitane
Pakisonal
Parales
Parcisol
Pargitan
Parkin
Parkinane
Parkines
Parkinidyl
Parkisan
Parkitane
Parkizol
Tonaril
Trihexifenidilo
Trihexylphenidyl
Trihexylphenidyle
Trihexylphenizyl
Trihexyphenidyle
Trihexyphenidylum
Triphenidyl
Chemical FormulaC20H31NO
Average Molecular Mass301.466 g/mol
Monoisotopic Mass301.241 g/mol
CAS Registry Number144-11-6
IUPAC Name1-cyclohexyl-1-phenyl-3-(piperidin-1-yl)propan-1-ol
Traditional Nametrihexyphenidyl
SMILESOC(CCN1CCCCC1)(C1CCCCC1)C1=CC=CC=C1
InChI IdentifierInChI=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 KeyInChIKey=HWHLPVGTWGOCJO-UHFFFAOYNA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassOrganic nitrogen compounds
ClassOrganonitrogen compounds
Sub ClassAmines
Direct ParentAralkylamines
Alternative Parents
Substituents
  • Aralkylamine
  • Monocyclic benzene moiety
  • Piperidine
  • Benzenoid
  • 1,3-aminoalcohol
  • Tertiary alcohol
  • Tertiary amine
  • Tertiary aliphatic amine
  • Azacycle
  • Organoheterocyclic compound
  • Alcohol
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organopnictogen compound
  • Aromatic alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point258.5°C
Boiling PointNot Available
Solubility3.14e-03 g/L
LogP4.49
Predicted Properties
PropertyValueSource
Water Solubility0.0031 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity93.21 m³·mol⁻¹ChemAxon
Polarizability36.73 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4j-9520000000-9a2c379908fc40e03fe2View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-08gm-8291000000-e91e4f7026454f2df547View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0udi-4119000000-9ed82688d3c1b39f26ebView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0f89-1096000000-d3df91688ef1945d673eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-9130000000-5c5ffd9794999341adecView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05mn-9210000000-f0b1224b58d81bff09deView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0019000000-7ed6535dacec03b4f64eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0f89-9145000000-5ef99bbb769978df62bdView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-9010000000-ee7ed12c77da3bd0134fView in MoNA
MSMass Spectrum (Electron Ionization)splash10-0002-9200000000-2092a098302f5e63b76cView in MoNA
Toxicity Profile
Route of ExposureOral. Trihexyphenidyl is rapidly absorbed from the gastrointestinal tract.
Mechanism of ToxicityTrihexyphenidyl 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.
MetabolismHalf Life: 3.3-4.1 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesIndicated for the treatment of parkinson's disease and extrapyramidal reactions caused by drugs.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms 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.
TreatmentTreatment of acute overdose involves symptomatic and supportive therapy. Gastric lavage or other methods to limit absorption should be instituted. A small dose of diazepam or a short-acting barbiturate may be administered if CNS excitation is observed. Phenothiazines are contraindicated because the toxicity may be intensified due to their antimuscarinic action, causing coma. Respiratory support, artificial respiration or vasopressor agents may be necessary. Hyperpyrexia must be reversed, fluid volume replaced and acid-balance maintained. Urinary catheterization may be necessary. It is not known if Trihexyphenidyl is dialyzable. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00376
HMDB IDHMDB14520
PubChem Compound ID5572
ChEMBL IDCHEMBL1490
ChemSpider ID5371
KEGG IDC07171
UniProt IDNot Available
OMIM ID
ChEBI ID518411
BioCyc IDNot Available
CTD IDNot Available
Stitch IDTrihexyphenidyl
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkTrihexyphenidyl
References
Synthesis ReferenceNot Available
MSDST3D2770.pdf
General References
  1. Drugs.com [Link]
  2. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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 action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.007 uMNot AvailableBindingDB 81462
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. [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. [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. [3208836 ]
  4. Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]
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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular Weight:
66127.445 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0064 uMNot AvailableBindingDB 81462
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. [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. [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. [3208836 ]
  4. Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]
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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0016 uMNot AvailableBindingDB 81462
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. [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. [17016423 ]
  3. Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]
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 action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:
CHRM4
Uniprot ID:
P08173
Molecular Weight:
53048.65 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0026 uMNot AvailableBindingDB 81462
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. [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. [1994002 ]
  3. Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]
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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM5
Uniprot ID:
P08912
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. [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. [1994002 ]