Identification

Name
Hexocyclium
Accession Number
DB06787
Type
Small Molecule
Groups
Approved
Description

Hexocyclium is a muscarinic acetylcholine receptor antagonist which was presumably used in the treatment of gastric ulcer or diarrhea. It was once available under the tradename Tral marketed by Abbvie Inc. but has been discontinued. Proton pump inhibitors like Omeprazole and opiate anti-diarrheal agents like Loperamide have largely replaced the use of anti-muscarinics in the treatment of gastric ulcers and diarrhea due to their more favorable side effect profiles.

Structure
Thumb
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Hexocyclium methylsulfate84OPZ2Q0VB115-63-9NSILVESQCSUIAJ-UHFFFAOYSA-M
International/Other Brands
Tral (Abbott) / Traline (Abbott)
Categories
UNII
LL3147PI1T
CAS number
6004-98-4
Weight
Average: 317.496
Monoisotopic: 317.258740111
Chemical Formula
C20H33N2O
InChI Key
ZRYHPQCHHOKSMD-UHFFFAOYSA-N
InChI
InChI=1S/C20H33N2O/c1-22(2)15-13-21(14-16-22)17-20(23,18-9-5-3-6-10-18)19-11-7-4-8-12-19/h3,5-6,9-10,19,23H,4,7-8,11-17H2,1-2H3/q+1
IUPAC Name
4-(2-cyclohexyl-2-hydroxy-2-phenylethyl)-1,1-dimethylpiperazin-1-ium
SMILES
C[N+]1(C)CCN(CC(O)(C2CCCCC2)C2=CC=CC=C2)CC1

Pharmacology

Indication

The World Health Organization classifies hexocyclium as a drug for functional gastrointestinal disorders 5. Like other anti-muscarinic agents, hexocyclium was likely used to treat peptic ulcers or diarrhea.

Pharmacodynamics

Hexocyclium reduces gastrointesitinal motility and gastric acid secretion 2,3.

Mechanism of action

Hexocyclium binds to and inhibits muscarinic acetylcholine receptors 1. This decreases gastric acid secretion by preventing the activation of M3 receptors on pareital cells and subsequent stimulation of gastric acid secretion 4. The antagonism of M3 receptors in the intestine inhibits smooth muscle contraction resulting in a decrease in motility. The binding of hexocyclium to other muscarinic receptor types produces typical anti-muscarinic side effects.

TargetActionsOrganism
UMuscarinic acetylcholine receptor M1
antagonist
Humans
UMuscarinic acetylcholine receptor M2
antagonist
Humans
AMuscarinic acetylcholine receptor M3
antagonist
Humans
UMuscarinic acetylcholine receptor M4
antagonist
Humans
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
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Hexocyclium can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of Tachycardia can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Hexocyclium.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may increase the central nervous system depressant (CNS depressant) activities of Hexocyclium.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Hexocyclium.
4-Methoxyamphetamine4-Methoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Hexocyclium.
5-methoxy-N,N-dimethyltryptamine5-methoxy-N,N-dimethyltryptamine may increase the central nervous system depressant (CNS depressant) activities of Hexocyclium.
7-Nitroindazole7-Nitroindazole may increase the central nervous system depressant (CNS depressant) activities of Hexocyclium.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the central nervous system depressant (CNS depressant) activities of Hexocyclium.
AbediterolThe risk or severity of Tachycardia can be increased when Hexocyclium is combined with Abediterol.
AcepromazineAcepromazine may increase the central nervous system depressant (CNS depressant) activities of Hexocyclium.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

Synthesis Reference

U.S. Patent 2,907,765.

General References
  1. Waelbroeck M, Camus J, Tastenoy M, Feifel R, Mutschler E, Tacke R, Strohmann C, Rafeiner K, Rodrigues de Miranda JF, Lambrecht G: Binding and functional properties of hexocyclium and sila-hexocyclium derivatives to muscarinic receptor subtypes. Br J Pharmacol. 1994 Jun;112(2):505-14. [PubMed:8075869]
  2. KASICH AM, FEIN HD: Hexocyclium methosulfate in active duodenal ulcer; evaluation of a new anticholinergic drug in conventional and long-acting forms, especially its effect on gastric pH as studied in 48-hour analysis. Am J Dig Dis. 1958 Jan;3(1):12-23. [PubMed:13487546]
  3. Grundhofer B, Gibaldi M: Biopharmaceutic factors that influence effects of anticholinergic drugs: comparison of propantheline, hexocyclium, and isopropamide. J Pharm Sci. 1977 Oct;66(10):1433-5. [PubMed:21951]
  4. Rang, H. P. and Dale, M. M. (2012). Rang and Dale's Pharmacology (7th ed.). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  5. WHOCC-ATC: Hexocyclium [Link]
External Links
KEGG Compound
C07811
PubChem Compound
24199
PubChem Substance
310264885
ChemSpider
22621
BindingDB
81959
RxNav
26867
ChEBI
5707
ChEMBL
CHEMBL1201325
Wikipedia
Hexocyclium
ATC Codes
A03AB10 — Hexocyclium
MSDS
Download (671 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)203-204U.S. Patent 2,907,765.
Predicted Properties
PropertyValueSource
Water Solubility0.000576 mg/mLALOGPS
logP-1.1ALOGPS
logP-0.99ChemAxon
logS-5.8ALOGPS
pKa (Strongest Acidic)13.51ChemAxon
pKa (Strongest Basic)4.95ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area23.47 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity108.16 m3·mol-1ChemAxon
Polarizability38.29 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-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
N-methylpiperazines / Benzene and substituted derivatives / Tetraalkylammonium salts / Tertiary alcohols / Trialkylamines / 1,2-aminoalcohols / Azacyclic compounds / Organopnictogen compounds / Organic salts / Hydrocarbon derivatives
show 2 more
Substituents
N-methylpiperazine / N-alkylpiperazine / Aralkylamine / Monocyclic benzene moiety / 1,4-diazinane / Piperazine / Benzenoid / Tetraalkylammonium salt / Quaternary ammonium salt / Tertiary alcohol
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
amine (CHEBI:5707)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Waelbroeck M, Camus J, Tastenoy M, Feifel R, Mutschler E, Tacke R, Strohmann C, Rafeiner K, Rodrigues de Miranda JF, Lambrecht G: Binding and functional properties of hexocyclium and sila-hexocyclium derivatives to muscarinic receptor subtypes. Br J Pharmacol. 1994 Jun;112(2):505-14. [PubMed:8075869]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Waelbroeck M, Camus J, Tastenoy M, Feifel R, Mutschler E, Tacke R, Strohmann C, Rafeiner K, Rodrigues de Miranda JF, Lambrecht G: Binding and functional properties of hexocyclium and sila-hexocyclium derivatives to muscarinic receptor subtypes. Br J Pharmacol. 1994 Jun;112(2):505-14. [PubMed:8075869]
Kind
Protein
Organism
Humans
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. Waelbroeck M, Camus J, Tastenoy M, Feifel R, Mutschler E, Tacke R, Strohmann C, Rafeiner K, Rodrigues de Miranda JF, Lambrecht G: Binding and functional properties of hexocyclium and sila-hexocyclium derivatives to muscarinic receptor subtypes. Br J Pharmacol. 1994 Jun;112(2):505-14. [PubMed:8075869]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
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...
Gene Name
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
Molecular Weight
53048.65 Da
References
  1. Waelbroeck M, Camus J, Tastenoy M, Feifel R, Mutschler E, Tacke R, Strohmann C, Rafeiner K, Rodrigues de Miranda JF, Lambrecht G: Binding and functional properties of hexocyclium and sila-hexocyclium derivatives to muscarinic receptor subtypes. Br J Pharmacol. 1994 Jun;112(2):505-14. [PubMed:8075869]

Drug created on September 14, 2010 10:21 / Updated on March 01, 2020 23:32

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