You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameAlverine
Accession NumberDB01616
TypeSmall Molecule
GroupsApproved
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
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AudmonalNot Available
ProfenilNot Available
SpasmaverineNot Available
SpasmonalNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Alverine citrate
5560-59-8
Thumb
  • InChI Key: RYHCACJBKCOBTJ-UHFFFAOYSA-N
  • Monoisotopic Mass: 473.241352479
  • Average Mass: 473.5586
DBSALT000008
Categories
UNII46TIR1560O
CAS number150-59-4
WeightAverage: 281.4351
Monoisotopic: 281.214349869
Chemical FormulaC20H27N
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylpropylamines
Direct ParentPhenylpropylamines
Alternative Parents
Substituents
  • Phenylpropylamine
  • Aralkylamine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed 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.
PharmacodynamicsAlverine 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 actionNot Available
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

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

Route of eliminationHigh renal clearance of all metabolites indicating that they are eliminated by active renal secretion.
Half lifeThe plasma half-life averages 0.8 hours for alverine and 5.7 hours for the active primary metabolite.
ClearanceNot Available
ToxicityCan produce hypotension and atropine-like toxic effects. Fatality has occurred following overdose with very high doses.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point< 25 °CPhysProp
boiling point212.5 °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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesA03AX08A03AX58
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

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 signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G pro...
Gene Name:
HTR1A
Uniprot ID:
P08908
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 ]
Comments
comments powered by Disqus
Drug created on August 29, 2007 14:13 / Updated on September 16, 2013 17:15