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Identification
NameTrihexyphenidyl
Accession NumberDB00376  (APRD00070)
Typesmall molecule
Groupsapproved
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
SynonymLanguageCode
(RS)-1-cyclohexyl-1-phenyl-3-(1-piperidyl)propan-1-olNot AvailableIUPAC
Benzhexol HydrochlorideNot AvailableIS
TrihexifenidiloSpanishINN
TrihexyphenidylNot AvailableBAN
TrihexyphénidyleFrenchDCF
TrihexyphenidylumLatinINN
Salts
Name/CAS Structure Properties
Trihexyphenidyl Hydrochloride
Thumb
  • InChI Key: QDWJJTJNXAKQKD-UHFFFAOYNA-N
  • Monoisotopic Mass: 337.217242358
  • Average Mass: 337.927
DBSALT000448
Brand names
NameCompany
ACAAtlantic
AcamedMedifive
AltantPanbiotic
ArtaneSanofi Aventis
ArtineThe Central
AtanNewai Chem
BenzhexolJohnson
BenzoxLi Ta
BexolIntas
BroflexAlliance
CyclodolGrindeks
DyskinilCrescent
Ea TenHeng Hsin
HexymerMersifarma
HipokinonPsicofarma
LahexyLa Pharmaceuticals
PacitaneWyeth
PakisonalTakata Seiyaku
ParalesPsyco Remedies
ParcisolMilve
PargitanNevada Pharma
ParkinMicro Synapse
ParkinaneEisai
ParkinesTowa Yakuhin
ParkinidylCCPC
ParkisanBalkanpharma
ParkitaneSun
ParkizolHikma
TonarilChile
Brand mixtures
Brand NameIngredients
Hexiflu-TTrihexyphenidyl and Trifluoperazine
Krisp-TTrihexyphenidyl and Risperidone
Lacalm PlusTrihexyphenidyl and Trifluoperazine
Categories
CAS number144-11-6
WeightAverage: 301.4662
Monoisotopic: 301.240564619
Chemical FormulaC20H31NO
InChI KeyHWHLPVGTWGOCJO-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenylpropylamines
Direct parentPhenylpropylamines
Alternative parentsPiperidines; Tertiary Alcohols; Tertiary Amines; Polyamines
Substituentspiperidine; tertiary alcohol; tertiary amine; polyamine; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the phenylpropylamines. These are compounds containing a phenylpropylamine moiety, which consists of a phenyl group substituted at the third carbon by an propan-1-amine.
Pharmacology
IndicationIndicated for the treatment of parkinson's disease and extrapyramidal reactions caused by drugs.
PharmacodynamicsTrihexyphenidyl 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 actionTrihexyphenidyl 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.
AbsorptionTrihexyphenidyl is rapidly absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half life3.3-4.1 hours
ClearanceNot Available
ToxicitySymptoms 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9156
Blood Brain Barrier + 0.9523
Caco-2 permeable + 0.6707
P-glycoprotein substrate Substrate 0.6943
P-glycoprotein inhibitor I Inhibitor 0.5993
P-glycoprotein inhibitor II Non-inhibitor 0.7561
Renal organic cation transporter Inhibitor 0.7563
CYP450 2C9 substrate Non-substrate 0.8256
CYP450 2D6 substrate Non-substrate 0.7655
CYP450 3A4 substrate Non-substrate 0.5746
CYP450 1A2 substrate Non-inhibitor 0.9187
CYP450 2C9 substrate Non-inhibitor 0.9126
CYP450 2D6 substrate Inhibitor 0.8966
CYP450 2C19 substrate Non-inhibitor 0.9248
CYP450 3A4 substrate Non-inhibitor 0.8506
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9543
Ames test Non AMES toxic 0.8434
Carcinogenicity Non-carcinogens 0.9238
Biodegradation Not ready biodegradable 0.9253
Rat acute toxicity 2.6751 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Strong inhibitor 0.6676
hERG inhibition (predictor II) Inhibitor 0.5713
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
Dosage forms
FormRouteStrength
ElixirOral
TabletOral
Prices
Unit descriptionCostUnit
Trihexyphenidyl HCl 5 mg tablet0.37USDtablet
Trihexyphenidyl 5 mg tablet0.36USDtablet
Trihexyphenidyl HCl 2 mg tablet0.26USDtablet
Trihexyphenidyl 2 mg tablet0.18USDtablet
Apo-Trihex 5 mg Tablet0.07USDtablet
Apo-Trihex 2 mg Tablet0.04USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point258.5 °CNot Available
logP4.49SANGSTER (1993)
Predicted Properties
PropertyValueSource
water solubility3.14e-03 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 area23.47ChemAxon
rotatable bond count5ChemAxon
refractivity93.21ChemAxon
polarizability36.73ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07171
PubChem Compound5572
PubChem Substance46507717
ChemSpider5371
Therapeutic Targets DatabaseDAP001532
PharmGKBPA164747026
Drug Product Database726265
RxListhttp://www.rxlist.com/cgi/generic3/trihexyphen.htm
Drugs.comhttp://www.drugs.com/cdi/trihexyphenidyl.html
WikipediaTrihexyphenidyl
ATC CodesN04AA01
AHFS Codes
  • 12:08.04
PDB EntriesNot Available
FDA labelshow(197 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
DonepezilPossible antagonism of action
GalantaminePossible antagonism of action
HaloperidolThe anticholinergic increases the risk of psychosis and tardive dyskinesia
Potassium ChlorideThe 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.
PramlintideThe 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.
RivastigminePossible antagonism of action
SecretinThe 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.
TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Trihexyphenidyl, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
TrimethobenzamideTrimethobenzamide and Trihexyphenidyl, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
TriprolidineTriprolidine and Trihexyphenidyl, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
TrospiumTrospium and Trihexyphenidyl, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Food InteractionsNot Available

Targets

1. Muscarinic acetylcholine receptor M1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M1 P11229 Details

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
  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
  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. Epub 2008 Aug 7. Pubmed
  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
  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
  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
  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
  8. 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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M2 P08172 Details

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
  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
  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

3. Muscarinic acetylcholine receptor M3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M3 P20309 Details

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
  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
  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

4. Muscarinic acetylcholine receptor M4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M4 P08173 Details

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
  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

5. Muscarinic acetylcholine receptor M5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M5 P08912 Details

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
  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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:10