Identification

Name
Alverine
Accession Number
DB01616
Type
Small Molecule
Groups
Approved, Investigational
Description

Alverine is a smooth muscle relaxant. Smooth muscle is a type of muscle that is not under voluntary control; it is the muscle present in places such as the gut and uterus. Alverine acts directly on the muscle in the gut, causing it to relax. This prevents the muscle spasms which occur in the gut in conditions such as irritable bowel syndrome and diverticular disease. It is used to relieve cramps or spasms of the stomach and intestines. It is also useful in treating irritable bowel syndrome (IBS) and similar conditions. It can also be used to help relieve period pain. Alverine is formulated as the citrate salt (5982-87-6).

Structure
Thumb
Synonyms
  • Alverina
  • Alverinum
  • Bis(gamma-phenylpropyl)ethylamine
  • Di(phenylpropyl)ethylamine
  • N-Ethyl-3-phenyl-N-(3-phenylpropyl)-1-propanamine
  • N-Ethyl-3,3'-diphenyldipropylamine
  • N-Ethyl-N-(3-phenylpropyl)benzenepropanamine
  • N,N-Bis(3-phenylpropyl)ethylamine
  • Phenopropamine
  • Phenpropamine
Product Ingredients
IngredientUNIICASInChI Key
Alverine citrate9JFB58YK1E5560-59-8RYHCACJBKCOBTJ-UHFFFAOYSA-N
International/Other Brands
Audmonal / Profenil / Spasmaverine / Spasmonal
Categories
UNII
46TIR1560O
CAS number
150-59-4
Weight
Average: 281.4351
Monoisotopic: 281.214349869
Chemical Formula
C20H27N
InChI Key
ZPFXAOWNKLFJDN-UHFFFAOYSA-N
InChI
InChI=1S/C20H27N/c1-2-21(17-9-15-19-11-5-3-6-12-19)18-10-16-20-13-7-4-8-14-20/h3-8,11-14H,2,9-10,15-18H2,1H3
IUPAC Name
ethylbis(3-phenylpropyl)amine
SMILES
CCN(CCCC1=CC=CC=C1)CCCC1=CC=CC=C1

Pharmacology

Indication

Used to relieve cramps or spasms of the stomach and intestines. It is also useful in treating irritable bowel syndrome (IBS) and similar conditions. It can also be used to help relieve period pain. Alverine citrate is also under investigation to increase the cytotoxic effects of the proteasome inhibitor MG132 on breast cancer cells.

Pharmacodynamics

Alverine is a smooth muscle relaxant. Smooth muscle is a type of muscle that is not under voluntary control; it is the muscle present in places such as the gut and uterus. Alverine acts directly on the muscle in the gut, causing it to relax. This prevents the muscle spasms which occur in the gut in conditions such as irritable bowel syndrome and diverticular disease. Diverticular disease is a condition in which small pouches form in the gut lining. These pouches can trap particles of food and become inflamed and painful. In irritable bowel syndrome the normal activity of the gut muscle is lost. The muscle spasms result in symptoms such as heartburn, abdominal pain and bloating, constipation or diarrhoea. By relaxing the gut muscle, alverine citrate relieves the symptoms of this condition. Alverine also relaxes the smooth muscle in the womb (uterus). It is therefore also used to treat painful menstruation, which is caused by muscle spasms in the uterus (dysmenorrhea).

Mechanism of action
TargetActionsOrganism
A5-hydroxytryptamine receptor 1A
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Rapidly converted to its primary active metabolite, which is then further converted to two secondary metabolites.

Route of elimination

High renal clearance of all metabolites indicating that they are eliminated by active renal secretion.

Half life

The plasma half-life averages 0.8 hours for alverine and 5.7 hours for the active primary metabolite.

Clearance
Not Available
Toxicity

Can produce hypotension and atropine-like toxic effects. Fatality has occurred following overdose with very high doses.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Alverine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Alverine is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Alverine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Alverine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Alverine.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Alverine is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Alverine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Alverine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Alverine is combined with 7-Nitroindazole.
AcenocoumarolThe risk or severity of adverse effects can be increased when Alverine is combined with Acenocoumarol.
Food Interactions
Not Available

References

General References
  1. Hayase M, Hashitani H, Suzuki H, Kohri K, Brading AF: Evolving mechanisms of action of alverine citrate on phasic smooth muscles. Br J Pharmacol. 2007 Dec;152(8):1228-38. Epub 2007 Oct 15. [PubMed:17934514]
  2. Wittmann T, Paradowski L, Ducrotte P, Bueno L, Andro Delestrain MC: Clinical trial: the efficacy of alverine citrate/simeticone combination on abdominal pain/discomfort in irritable bowel syndrome--a randomized, double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2010 Mar;31(6):615-24. doi: 10.1111/j.1365-2036.2009.04216.x. Epub 2009 Dec 10. [PubMed:20003095]
  3. Ju D, Wang X, Xie Y: Dyclonine and alverine citrate enhance the cytotoxic effects of proteasome inhibitor MG132 on breast cancer cells. Int J Mol Med. 2009 Feb;23(2):205-9. [PubMed:19148544]
  4. Spasmonal Package Insert [Link]
External Links
Human Metabolome Database
HMDB0015554
KEGG Drug
D07440
PubChem Compound
3678
PubChem Substance
46506981
ChemSpider
3550
BindingDB
37636
ChEBI
518413
ChEMBL
CHEMBL253371
PharmGKB
PA164764505
Wikipedia
Alverine
ATC Codes
A03AX58 — Alverine, combinationsA03AX08 — Alverine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentIrritable Bowel Syndrome (IBS)1

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)< 25 °CPhysProp
boiling point (°C)212.5 °C at 1.30E+01 mm HgPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.00096 mg/mLALOGPS
logP5.73ALOGPS
logP5.46ChemAxon
logS-5.5ALOGPS
pKa (Strongest Basic)10.44ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity92.67 m3·mol-1ChemAxon
Polarizability35.42 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9925
Blood Brain Barrier+0.9482
Caco-2 permeable+0.8219
P-glycoprotein substrateSubstrate0.6368
P-glycoprotein inhibitor INon-inhibitor0.6741
P-glycoprotein inhibitor IINon-inhibitor0.853
Renal organic cation transporterInhibitor0.7848
CYP450 2C9 substrateNon-substrate0.7873
CYP450 2D6 substrateSubstrate0.5452
CYP450 3A4 substrateNon-substrate0.6521
CYP450 1A2 substrateInhibitor0.6458
CYP450 2C9 inhibitorNon-inhibitor0.9308
CYP450 2D6 inhibitorInhibitor0.8368
CYP450 2C19 inhibitorInhibitor0.5919
CYP450 3A4 inhibitorNon-inhibitor0.8074
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5739
Ames testNon AMES toxic0.9653
CarcinogenicityNon-carcinogens0.6473
BiodegradationNot ready biodegradable0.9649
Rat acute toxicity2.6539 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6077
hERG inhibition (predictor II)Inhibitor0.7442
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
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpropylamines. These are compounds containing a phenylpropylamine moiety, which consists of a phenyl group substituted at the third carbon by an propan-1-amine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylpropylamines
Direct Parent
Phenylpropylamines
Alternative Parents
Aralkylamines / Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phenylpropylamine / Aralkylamine / Tertiary aliphatic amine / Tertiary amine / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound / Amine / Aromatic homomonocyclic compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
tertiary amine (CHEBI:518413)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Coelho AM, Jacob L, Fioramonti J, Bueno L: Rectal antinociceptive properties of alverine citrate are linked to antagonism at the 5-HT1A receptor subtype. J Pharm Pharmacol. 2001 Oct;53(10):1419-26. [PubMed:11697552]

Drug created on August 29, 2007 14:13 / Updated on November 02, 2018 08:30