Identification

Name
Tridihexethyl
Accession Number
DB00505  (APRD00286)
Type
Small Molecule
Groups
Withdrawn
Description

Tridihexethyl is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract. Tridihexethyl is an antimuscarinic, anticholinergic drug. Tridihexethyl is no longer available in the US market.

Structure
Thumb
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Tridihexethyl chloride25YK75CYMX4310-35-4XJGONMZLEDGBRM-UHFFFAOYSA-M
International/Other Brands
Pathilon / Propethonum
Categories
UNII
7HE50A367X
CAS number
60-49-1
Weight
Average: 318.5166
Monoisotopic: 318.279689779
Chemical Formula
C21H36NO
InChI Key
NPRHVSBSZMAEIN-UHFFFAOYSA-N
InChI
InChI=1S/C21H36NO/c1-4-22(5-2,6-3)18-17-21(23,19-13-9-7-10-14-19)20-15-11-8-12-16-20/h7,9-10,13-14,20,23H,4-6,8,11-12,15-18H2,1-3H3/q+1
IUPAC Name
(3-cyclohexyl-3-hydroxy-3-phenylpropyl)triethylazanium
SMILES
CC[N+](CC)(CC)CCC(O)(C1CCCCC1)C1=CC=CC=C1

Pharmacology

Indication

Used as an adjunct in the treatment of peptic ulcer disease and in Acquired nystagmus

Structured Indications
Not Available
Pharmacodynamics

Tridihexethyl is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract. Tridihexethyl is an antimuscarinic, anticholinergic drug.

Mechanism of action

Tridihexethyl binds the muscarinic acetylcholine receptor. It may block all three types of muscarinic receptors including M-1 receptors in the CNS and ganglia, M-2 receptors in the heart (vagus) and M-3 receptors at the parasympathetic NEJ system. The muscarinic acetylcholine receptors mediate various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Tridihexethyl inhibits vagally mediated reflexes by antagonizing the action of acetylcholine. This in turn reduces the secretion of gastric acids in the stomach.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M3
antagonist
Human
AMuscarinic acetylcholine receptor M1
antagonist
Human
AMuscarinic acetylcholine receptor M2
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB14648
KEGG Compound
C07861
PubChem Compound
20299
PubChem Substance
46506672
ChemSpider
19124
ChEBI
9701
ChEMBL
CHEMBL1201354
Therapeutic Targets Database
DAP000836
PharmGKB
PA164746229
ATC Codes
A03AB08 — Tridihexethyl

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Lederle laboratories div american cyanamid co
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)181.5 °CNot Available
water solubility11 mg/mLNot Available
logP1.17Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.68e-05 mg/mLALOGPS
logP2.31ALOGPS
logP0.29ChemAxon
logS-7.3ALOGPS
pKa (Strongest Acidic)13.69ChemAxon
pKa (Strongest Basic)-3.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity111.22 m3·mol-1ChemAxon
Polarizability39.17 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8291
Blood Brain Barrier+0.9277
Caco-2 permeable+0.6969
P-glycoprotein substrateSubstrate0.7363
P-glycoprotein inhibitor INon-inhibitor0.7804
P-glycoprotein inhibitor IINon-inhibitor0.6714
Renal organic cation transporterInhibitor0.5622
CYP450 2C9 substrateNon-substrate0.7795
CYP450 2D6 substrateNon-substrate0.5453
CYP450 3A4 substrateSubstrate0.5728
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9072
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9163
Ames testNon AMES toxic0.8549
CarcinogenicityNon-carcinogens0.5749
BiodegradationNot ready biodegradable0.9515
Rat acute toxicity2.5261 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5444
hERG inhibition (predictor II)Inhibitor0.8856
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
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

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
Benzene and substituted derivatives / Tetraalkylammonium salts / Tertiary alcohols / 1,3-aminoalcohols / Organopnictogen compounds / Organic salts / Hydrocarbon derivatives / Aromatic alcohols / Organic cations
Substituents
Aralkylamine / Monocyclic benzene moiety / Benzenoid / 1,3-aminoalcohol / Tetraalkylammonium salt / Quaternary ammonium salt / Tertiary alcohol / Organic oxygen compound / Alcohol / Aromatic alcohol
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
tertiary alcohol, quaternary ammonium ion (CHEBI:9701)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
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. 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]
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]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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. 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]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:23