Identification

Name
Papaverine
Accession Number
DB01113  (APRD00628, DB07725)
Type
Small Molecule
Groups
Approved, Investigational
Description

An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [PubChem]

Structure
Thumb
Synonyms
  • Mesotina
Product Ingredients
IngredientUNIICASInChI Key
Papaverine Codecarboxylate3RX65N0VN756896-69-6VTJFMXLVZKZSGE-UHFFFAOYSA-N
Papaverine Hydrochloride23473EC6BQ61-25-6UOTMYNBWXDUBNX-UHFFFAOYSA-N
Papaverine sulfate7A476JZB2T2053-26-1KYFCEOITJFJQGT-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Papaverine Hydrochloride Injection USPLiquid65 mgIntramuscular; Intravenous; SubcutaneousSandoz Canada Incorporated1951-12-31Not applicableCanada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Papaverine HydrochloridePapaverine Hydrochloride (30 mg/1mL)Injection, solutionIntramuscular; IntravenousClaris Lifesciences Limited2009-10-072010-11-04Us
Papaverine HydrochloridePapaverine Hydrochloride (30 mg/1mL)Injection, solutionIntramuscular; IntravenousClaris Lifesciences, Inc.2009-10-072010-11-04Us
Papaverine HydrochloridePapaverine Hydrochloride (30 mg/1mL)Injection, solutionIntramuscular; IntravenousSandoz2008-12-012008-12-31Us
Papaverine HydrochloridePapaverine Hydrochloride (30 mg/1mL)Injection, solutionIntramuscular; IntravenousClaris Lifesciences Limited2009-10-072010-11-04Us
Papaverine HydrochloridePapaverine Hydrochloride (30 mg/1mL)Injection, solutionIntravenousAMERICAN REGENT, INC.1995-09-012011-08-24Us
Papaverine HydrochloridePapaverine Hydrochloride (30 mg/1mL)Injection, solutionIntravenousAmerican Regent1995-09-01Not applicableUs
Papaverine HydrochloridePapaverine Hydrochloride (30 mg/1mL)Injection, solutionIntramuscular; IntravenousClaris Lifesciences, Inc.2009-10-072010-11-04Us
Papaverine HydrochloridePapaverine Hydrochloride (30 mg/1mL)Injection, solutionIntramuscular; IntravenousSandoz2008-12-012008-12-31Us
International/Other Brands
Alapav / Albatran / Artegodan / Cardioverina / Cerebid / Cerespan / Delapav / Dilaves / Dispamil / Drapavel / Durapav / Dynovas / Mesotina / Myobid / Optenyl / Pameion / Pamelon / Panergon / Papacon / Papalease / Papaversan / Papital T.R. / Paptial T.R. / Pavabid / Pavacap / Pavacen / Pavadel / Pavagen / Pavakey / Pavased / Pavatest / Paverolan / Paveron / Pavnell / Qua Bid / Ro-Papav / Therapav / Vasal / Vaso-Pav
Categories
UNII
DAA13NKG2Q
CAS number
58-74-2
Weight
Average: 339.385
Monoisotopic: 339.147058165
Chemical Formula
C20H21NO4
InChI Key
XQYZDYMELSJDRZ-UHFFFAOYSA-N
InChI
InChI=1S/C20H21NO4/c1-22-17-6-5-13(10-18(17)23-2)9-16-15-12-20(25-4)19(24-3)11-14(15)7-8-21-16/h5-8,10-12H,9H2,1-4H3
IUPAC Name
1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinoline
SMILES
COC1=C(OC)C=C(CC2=NC=CC3=CC(OC)=C(OC)C=C23)C=C1

Pharmacology

Indication

For the treatment of impotence and vasospasms.

Pharmacodynamics

Papaverine is a nonxanthine phosphodiesterase inhibitor for the relief of cerebral and peripheral ischemia associated with arterial spasm and myocardial ischemia complicated by arrhythmias. The main actions of Papaverine are exerted on cardiac and smooth muscle. Like qathidine, Papaverine acts directly on the heart muscle to depress conduction and prolong the refractory period. Papaverine relaxes various smooth muscles. This relaxation may be prominent if spasm exists. The muscle cell is not paralyzed by Papaverine and still responds to drugs and other stimuli causing contraction. The antispasmodic effect is a direct one, and unrelated to muscle innervation. Papaverine is practically devoid of effects on the central nervous system. Papaverine relaxes the smooth musculature of the larger blood vessels, especially coronary, systemic peripheral, and pulmonary arteries.

Mechanism of action

Perhaps by its direct vasodilating action on cerebral blood vessels, Papaverine increases cerebral blood flow and decreases cerebral vascular resistance in normal subjects; oxygen consumption is unaltered. These effects may explain the benefit reported from the drug in cerebral vascular encephalopathy.

TargetActionsOrganism
AcAMP-specific 3',5'-cyclic phosphodiesterase 4B
inhibitor
Human
UcAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

~90%

Metabolism
Not Available
Route of elimination
Not Available
Half life

0.5-2 hours

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

Interactions

Drug Interactions
DrugInteraction
AbexinostatThe risk or severity of QTc prolongation can be increased when Papaverine is combined with Abexinostat.
AcebutololThe risk or severity of QTc prolongation can be increased when Papaverine is combined with Acebutolol.
AceprometazineThe risk or severity of QTc prolongation can be increased when Papaverine is combined with Aceprometazine.
AcetyldigoxinThe risk or severity of QTc prolongation can be increased when Acetyldigoxin is combined with Papaverine.
AcrivastineThe risk or severity of QTc prolongation can be increased when Acrivastine is combined with Papaverine.
AdenosineThe risk or severity of QTc prolongation can be increased when Adenosine is combined with Papaverine.
AjmalineThe risk or severity of QTc prolongation can be increased when Ajmaline is combined with Papaverine.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Papaverine.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Papaverine.
AlimemazineThe risk or severity of QTc prolongation can be increased when Alimemazine is combined with Papaverine.
Food Interactions
Not Available

References

General References
  1. Tang Y, Luan J, Zhang X: Accelerating tissue expansion by application of topical papaverine cream. Plast Reconstr Surg. 2004 Oct;114(5):1166-9. [PubMed:15457029]
  2. Liu JK, Couldwell WT: Intra-arterial papaverine infusions for the treatment of cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2005;2(2):124-32. [PubMed:16159054]
  3. Takeuchi K, Sakamoto S, Nagayoshi Y, Nishizawa H, Matsubara J: Reactivity of the human internal thoracic artery to vasodilators in coronary artery bypass grafting. Eur J Cardiothorac Surg. 2004 Nov;26(5):956-9. [PubMed:15519189]
External Links
Human Metabolome Database
HMDB0015245
KEGG Drug
D07425
KEGG Compound
C06533
PubChem Compound
4680
PubChem Substance
46508003
ChemSpider
4518
BindingDB
14754
ChEBI
28241
ChEMBL
CHEMBL19224
Therapeutic Targets Database
DAP000959
PharmGKB
PA164745550
HET
EV1
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Papaverine
ATC Codes
G04BE02 — PapaverineG04BE52 — Papaverine, combinationsA03AD01 — Papaverine
AHFS Codes
  • 24:12.92 — Miscellaneous Vasodilatating Agents
PDB Entries
2wey / 3iak
MSDS
Download (74.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentProstatic Hyperplasia1
0TerminatedHealth Services ResearchCognitive Deficits / Schizophrenic Disorders1
2CompletedSupportive CareProstate Cancer1
3TerminatedTreatmentGastroenteritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Allergy Laboratories Inc.
  • Amend
  • American Regent
  • A-S Medication Solutions LLC
  • Ben Venue Laboratories Inc.
  • C.O. Truxton Inc.
  • Claris Lifesciences Inc.
  • Dispensing Solutions
  • Ebewe Pharma
  • Eon Labs
  • Hope Pharmaceuticals
  • Kaiser Foundation Hospital
  • Luitpold Pharmaceuticals Inc.
  • Major Pharmaceuticals
  • Meridian Medical Technologies Inc.
  • Physicians Total Care Inc.
  • Qualitest
  • Taylor Pharmaceuticals
  • Time-Cap Labs
Dosage forms
FormRouteStrength
Injection, solutionIntramuscular; Intravenous30 mg/1mL
Injection, solutionIntravenous30 mg/1mL
LiquidIntramuscular; Intravenous; Subcutaneous65 mg
Prices
Unit descriptionCostUnit
Papaverine 150 mg capsule sa1.86USD capsule
Papaverine 60 mg/2 ml vial1.68USD ml
Papaverine hcl powder0.76USD g
Para-time 150 mg capsule sa0.23USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)226 (dec) °CPhysProp
logP3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0129 mg/mLALOGPS
logP4.19ALOGPS
logP3.08ChemAxon
logS-4.4ALOGPS
pKa (Strongest Basic)6.03ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area49.81 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity95.52 m3·mol-1ChemAxon
Polarizability36.57 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9911
Blood Brain Barrier+0.9633
Caco-2 permeable+0.8866
P-glycoprotein substrateNon-substrate0.5389
P-glycoprotein inhibitor INon-inhibitor0.6485
P-glycoprotein inhibitor IINon-inhibitor0.8005
Renal organic cation transporterNon-inhibitor0.7229
CYP450 2C9 substrateNon-substrate0.796
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.6263
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8448
CYP450 2C19 inhibitorInhibitor0.778
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8558
Ames testNon AMES toxic0.689
CarcinogenicityNon-carcinogens0.9503
BiodegradationNot ready biodegradable0.9262
Rat acute toxicity2.9877 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9329
hERG inhibition (predictor II)Non-inhibitor0.7274
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
GC-MS Spectrum - EI-BGC-MSsplash10-0079-4569000000-42d74df972bf1280fb29
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
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0009000000-376bdab66f9ada8143f2
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0f6x-0049000000-fbf8945b1b40a8e629ff
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0779000000-37837168aff5cb2db6db
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-0019000000-175d5d7601656bade9be
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00dl-0569000000-1f7e7c97dcea64bf274a

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzylisoquinolines. These are organic compounds containing an isoquinoline to which a benzyl group is attached.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Isoquinolines and derivatives
Sub Class
Benzylisoquinolines
Direct Parent
Benzylisoquinolines
Alternative Parents
Dimethoxybenzenes / Phenoxy compounds / Anisoles / Alkyl aryl ethers / Pyridines and derivatives / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Hydrocarbon derivatives
Substituents
Benzylisoquinoline / O-dimethoxybenzene / Dimethoxybenzene / Phenoxy compound / Anisole / Phenol ether / Methoxybenzene / Alkyl aryl ether / Monocyclic benzene moiety / Pyridine
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzylisoquinoline alkaloid, dimethoxybenzene, isoquinolines (CHEBI:28241) / Isoquinoline alkaloids (C06533)

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. May be involved in mediating central nervous system effects of therapeutic agents ranging f...
Gene Name
PDE4B
Uniprot ID
Q07343
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4B
Molecular Weight
83342.695 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Xin ZC, Kim EK, Lin CS, Liu WJ, Tian L, Yuan YM, Fu J: Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian J Androl. 2003 Mar;5(1):15-8. [PubMed:12646997]
  4. Zhu S, Gan Z, Li Z, Liu Y, Yang X, Deng P, Xie Y, Yu M, Liao H, Zhao Y, Zhao L, Liao F: The measurement of cyclic nucleotide phosphodiesterase 4 activities via the quantification of inorganic phosphate with malachite green. Anal Chim Acta. 2009 Mar 16;636(1):105-10. doi: 10.1016/j.aca.2009.01.035. Epub 2009 Jan 22. [PubMed:19231363]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient wit...
Gene Name
PDE10A
Uniprot ID
Q9Y233
Uniprot Name
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
Molecular Weight
88411.71 Da
References
  1. Weber M, Breier M, Ko D, Thangaraj N, Marzan DE, Swerdlow NR: Evaluating the antipsychotic profile of the preferential PDE10A inhibitor, papaverine. Psychopharmacology (Berl). 2009 May;203(4):723-35. doi: 10.1007/s00213-008-1419-x. Epub 2008 Dec 9. [PubMed:19066855]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 13:32