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Identification
NameDrotaverine
Accession NumberDB06751
TypeSmall Molecule
GroupsApproved
DescriptionDrotaverine (INN, also known as drotaverin) is an antispasmodic drug, structurally related to papaverine. Drotaverine is a selective inhibitor of phosphodiesterase 4, and has no anticholinergic effects. Drotaverine has been shown to possess dose-dependant analgesic effects in animal models. One small study has shown drotaverine to be eliminated mainly non-renally.
Structure
Thumb
Synonyms
Drotaverin
Drotin
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
DrotinNot Available
No-SpaSanofi-Aventis
TaverinNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Drotaverine hydrochloride
985-12-6
Thumb
  • InChI Key: JBFLYOLJRKJYNV-MASIZSFYSA-N
  • Monoisotopic Mass: 433.2019862
  • Average Mass: 433.97
DBSALT000911
Categories
UNII98QS4N58TW
CAS number14009-24-6
WeightAverage: 397.5072
Monoisotopic: 397.225308485
Chemical FormulaC24H31NO4
InChI KeyOMFNSKIUKYOYRG-MOSHPQCFSA-N
InChI
InChI=1S/C24H31NO4/c1-5-26-21-10-9-17(14-22(21)27-6-2)13-20-19-16-24(29-8-4)23(28-7-3)15-18(19)11-12-25-20/h9-10,13-16,25H,5-8,11-12H2,1-4H3/b20-13-
IUPAC Name
(1Z)-1-[(3,4-diethoxyphenyl)methylidene]-6,7-diethoxy-1,2,3,4-tetrahydroisoquinoline
SMILES
CCOC1=C(OCC)C=C(\C=C2/NCCC3=CC(OCC)=C(OCC)C=C23)C=C1
Pharmacology
IndicationUsed in the treatment of functional bowel disorders and alleviating pain in renal colic.
Structured Indications Not Available
PharmacodynamicsDrotaverine is a spasmolytic agent by inhibiting PDE4 in smooth muscle cells.
Mechanism of actionDrotaverine inhibits phosphodiesterases hydrolysing cAMP, thereby increasing cAMP concentration, decreasing Ca uptake of the cells and changing the distribution of calcium among the cells. It may also have minor allosteric calcium channel blocking properties.
TargetKindPharmacological actionActionsOrganismUniProt ID
cAMP-specific 3',5'-cyclic phosphodiesterase 4AProteinyes
inhibitor
HumanP27815 details
Voltage-dependent L-type calcium channel subunit alpha-1CProteinunknown
inhibitor
HumanQ13936 details
Related Articles
AbsorptionBioavailability is highly variable
Volume of distributionNot Available
Protein binding80 to 95%
Metabolism

Hepatic

Route of eliminationNot Available
Half life7 to 12 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Bolaji OO, Onyeji CO, Ogundaini AO, Olugbade TA, Ogunbona FA: Pharmacokinetics and bioavailability of drotaverine in humans. Eur J Drug Metab Pharmacokinet. 1996 Jul-Sep;21(3):217-21. [PubMed:8980918 ]
External Links
ATC CodesA03AD02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9958
Blood Brain Barrier+0.753
Caco-2 permeable+0.6023
P-glycoprotein substrateSubstrate0.8447
P-glycoprotein inhibitor IInhibitor0.7972
P-glycoprotein inhibitor IINon-inhibitor0.8544
Renal organic cation transporterNon-inhibitor0.625
CYP450 2C9 substrateNon-substrate0.7958
CYP450 2D6 substrateNon-substrate0.6116
CYP450 3A4 substrateSubstrate0.6738
CYP450 1A2 substrateInhibitor0.6812
CYP450 2C9 inhibitorInhibitor0.5672
CYP450 2D6 inhibitorNon-inhibitor0.6789
CYP450 2C19 inhibitorNon-inhibitor0.6475
CYP450 3A4 inhibitorInhibitor0.7906
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8634
Ames testNon AMES toxic0.8205
CarcinogenicityNon-carcinogens0.9164
BiodegradationNot ready biodegradable0.9421
Rat acute toxicity2.5733 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6798
hERG inhibition (predictor II)Inhibitor0.7085
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 PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.002 mg/mLALOGPS
logP5.35ALOGPS
logP4.19ChemAxon
logS-5.3ALOGPS
pKa (Strongest Basic)7.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area48.95 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity117.99 m3·mol-1ChemAxon
Polarizability46.99 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as tetrahydroisoquinolines. These are tetrahydrogenated isoquinoline derivatives.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassTetrahydroisoquinolines
Sub ClassNot Available
Direct ParentTetrahydroisoquinolines
Alternative Parents
Substituents
  • Tetrahydroisoquinoline
  • Phenol ether
  • Aralkylamine
  • Alkyl aryl ether
  • Benzenoid
  • Monocyclic benzene moiety
  • Azacycle
  • Ether
  • Enamine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4A
Uniprot ID:
P27815
Molecular Weight:
98142.155 Da
References
  1. Muravyov AV, Yakusevich VV, Chuchkanov FA, Maimistova AA, Bulaeva SV, Zaitsev LG: Hemorheological efficiency of drugs, targeting on intracellular phosphodiesterase activity: in vitro study. Clin Hemorheol Microcirc. 2007;36(4):327-34. [PubMed:17502703 ]
  2. Romics I, Molnar DL, Timberg G, Mrklic B, Jelakovic B, Koszegi G, Blasko G: The effect of drotaverine hydrochloride in acute colicky pain caused by renal and ureteric stones. BJU Int. 2003 Jul;92(1):92-6. [PubMed:12823389 ]
  3. Pareek A, Chandurkar NB, Patil RT, Agrawal SN, Uday RB, Tambe SG: Efficacy and safety of aceclofenac and drotaverine fixed-dose combination in the treatment of primary dysmenorrhoea: a double-blind, double-dummy, randomized comparative study with aceclofenac. Eur J Obstet Gynecol Reprod Biol. 2010 Sep;152(1):86-90. doi: 10.1016/j.ejogrb.2010.05.007. Epub 2010 Jun 15. [PubMed:20554370 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belon...
Gene Name:
CACNA1C
Uniprot ID:
Q13936
Molecular Weight:
248974.1 Da
References
  1. Tomoskozi Z, Finance O, Aranyi P: Drotaverine interacts with the L-type Ca(2+) channel in pregnant rat uterine membranes. Eur J Pharmacol. 2002 Aug 2;449(1-2):55-60. [PubMed:12163106 ]
  2. Romics I, Molnar DL, Timberg G, Mrklic B, Jelakovic B, Koszegi G, Blasko G: The effect of drotaverine hydrochloride in acute colicky pain caused by renal and ureteric stones. BJU Int. 2003 Jul;92(1):92-6. [PubMed:12823389 ]
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Drug created on September 07, 2010 15:21 / Updated on August 17, 2016 12:24