Identification

Name
Drotaverine
Accession Number
DB06751
Type
Small Molecule
Groups
Approved, Investigational
Description

Drotaverine (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
Product Ingredients
IngredientUNIICASInChI Key
Drotaverine hydrochloride24ZVH4C669985-12-6JBFLYOLJRKJYNV-MASIZSFYSA-N
International/Other Brands
Drotin / No-Spa (Sanofi-Aventis) / Taverin
Categories
UNII
98QS4N58TW
CAS number
14009-24-6
Weight
Average: 397.5072
Monoisotopic: 397.225308485
Chemical Formula
C24H31NO4
InChI Key
OMFNSKIUKYOYRG-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

Indication

Used in the treatment of functional bowel disorders and alleviating pain in renal colic.

Pharmacodynamics

Drotaverine is a spasmolytic agent by inhibiting PDE4 in smooth muscle cells.

Mechanism of action

Drotaverine 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.

TargetActionsOrganism
AcAMP-specific 3',5'-cyclic phosphodiesterase 4A
inhibitor
Human
UVoltage-dependent L-type calcium channel subunit alpha-1C
inhibitor
Human
Absorption

Bioavailability is highly variable

Volume of distribution
Not Available
Protein binding

80 to 95%

Metabolism

Hepatic

Route of elimination
Not Available
Half life

7 to 12 hours

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
  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
Human Metabolome Database
HMDB0015669
PubChem Compound
1712095
PubChem Substance
99443287
ChemSpider
1361582
ChEBI
135630
ChEMBL
CHEMBL551978
PharmGKB
PA165958398
Wikipedia
Drotaverine
ATC Codes
A03AD02 — Drotaverine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Unknown StatusDiagnosticEffect of Meperidine or Drotaverine on Effacement and Dilatation of the Cervix During Labor in Full Term Primigravidae1
2, 3CompletedTreatmentFailure of Cervical Dilation as Antepartum Condition / Labour Pain / Mild Birth Asphyxia, APGAR 4-7 / Prolonged First Stage of Labor1
3CompletedPreventionBile Duct Diseases / ERCP / Pancreatic Diseases1
4TerminatedTreatmentDysmenorrhea1

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
Not 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 RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

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 tetrahydroisoquinolines. These are tetrahydrogenated isoquinoline derivatives.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Tetrahydroisoquinolines
Sub Class
Not Available
Direct Parent
Tetrahydroisoquinolines
Alternative Parents
Phenoxy compounds / Phenol ethers / Aralkylamines / Alkyl aryl ethers / Enamines / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Tetrahydroisoquinoline / Phenoxy compound / Phenol ether / Alkyl aryl ether / Aralkylamine / Monocyclic benzene moiety / Benzenoid / Secondary aliphatic amine / Enamine / Ether
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not 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
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
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, hor...
Gene Name
CACNA1C
Uniprot ID
Q13936
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1C
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]

Drug created on September 07, 2010 15:21 / Updated on August 02, 2018 07:46