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.

Structure

Similar Structures

Synonyms

Papaverina
Papaverine

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Papaverine codecarboxylate	3RX65N0VN7	56896-69-6	VTJFMXLVZKZSGE-UHFFFAOYSA-N
Papaverine hydrochloride	23473EC6BQ	61-25-6	UOTMYNBWXDUBNX-UHFFFAOYSA-N
Papaverine sulfate	7A476JZB2T	2053-26-1	KYFCEOITJFJQGT-UHFFFAOYSA-N

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Papaverine Hydrochloride Injection USP	Liquid	65 mg	Intramuscular; Intravenous; Subcutaneous	Sandoz Canada Incorporated	1951-12-31	Not applicable

Unapproved/Other Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Papaverine Hydrochloride	Papaverine hydrochloride (30 mg/1mL)	Injection, solution	Intramuscular; Intravenous	Claris Lifesciences Limited	2009-10-07	2010-11-04
Papaverine Hydrochloride	Papaverine hydrochloride (30 mg/1mL)	Injection, solution	Intravenous	AMERICAN REGENT, INC.	1995-09-01	Not applicable
Papaverine Hydrochloride	Papaverine hydrochloride (30 mg/1mL)	Injection, solution	Intramuscular; Intravenous	Claris Lifesciences Limited	2009-10-07	2010-11-04
Papaverine Hydrochloride	Papaverine hydrochloride (30 mg/1mL)	Injection, solution	Intravenous	AMERICAN REGENT, INC.	1995-09-01	2011-08-24
Papaverine Hydrochloride	Papaverine hydrochloride (30 mg/1mL)	Injection, solution	Intramuscular; Intravenous	Sandoz	2008-12-01	2008-12-31
Papaverine Hydrochloride	Papaverine hydrochloride (30 mg/1mL)	Injection, solution	Intramuscular; Intravenous	Claris Lifesciences, Inc.	2009-10-07	2010-11-04
Papaverine Hydrochloride	Papaverine hydrochloride (30 mg/1mL)	Injection, solution	Intramuscular; Intravenous	Claris Lifesciences, Inc.	2009-10-07	2010-11-04
Papaverine Hydrochloride	Papaverine hydrochloride (30 mg/1mL)	Injection, solution	Intramuscular; Intravenous	Sandoz	2008-12-01	2008-12-31

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.

Target	Actions	Organism
AcAMP-specific 3',5'-cyclic phosphodiesterase 4B	inhibitor	Humans
UcAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	inhibitor	Humans

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

Drug	Interaction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid	The therapeutic efficacy of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid can be increased when used in combination with Papaverine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline	7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the orthostatic hypotensive activities of Papaverine.
Abexinostat	The risk or severity of QTc prolongation can be increased when Papaverine is combined with Abexinostat.
Acebutolol	The risk or severity of QTc prolongation can be increased when Papaverine is combined with Acebutolol.
Aceprometazine	The risk or severity of QTc prolongation can be increased when Papaverine is combined with Aceprometazine.
Acetyldigoxin	The risk or severity of QTc prolongation can be increased when Acetyldigoxin is combined with Papaverine.
Acrivastine	The risk or severity of QTc prolongation can be increased when Acrivastine is combined with Papaverine.
Adenosine	The risk or severity of QTc prolongation can be increased when Adenosine is combined with Papaverine.
Ajmaline	The risk or severity of QTc prolongation can be increased when Ajmaline is combined with Papaverine.
Aldesleukin	The risk or severity of adverse effects can be increased when Aldesleukin is combined with Papaverine.

Food Interactions

Not Available

References

General References

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]
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]
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 — Papaverine

A03AD01 — Papaverine

G04BE52 — Papaverine, combinations

AHFS Codes

24:12.92 — Miscellaneous Vasodilatating Agents

PDB Entries

2wey / 3iak

MSDS

Download (74.4 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Not Yet Recruiting	Treatment	Prostatic Hyperplasia	1
0	Terminated	Health Services Research	Cognitive Deficits / Schizophrenic Disorders	1
1	Recruiting	Treatment	Lung Non-Small Cell Carcinoma	1
2	Completed	Supportive Care	Prostate Cancer	1
3	Terminated	Treatment	Gastroenteritis	1
4	Not Yet Recruiting	Prevention	Anaesthesia therapy / Pediatrics / Vasospasm	1

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

Form	Route	Strength
Injection, solution	Intramuscular; Intravenous	30 mg/1mL
Injection, solution	Intravenous	30 mg/1mL
Liquid	Intramuscular; Intravenous; Subcutaneous	65 mg

Prices

Unit description	Cost	Unit
Papaverine 150 mg capsule sa	1.86USD	capsule
Papaverine 60 mg/2 ml vial	1.68USD	ml
Papaverine hcl powder	0.76USD	g
Para-time 150 mg capsule sa	0.23USD	capsule

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	226 (dec) °C	PhysProp
logP	3	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0129 mg/mL	ALOGPS
logP	4.19	ALOGPS
logP	3.08	ChemAxon
logS	-4.4	ALOGPS
pKa (Strongest Basic)	6.03	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	49.81 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	95.52 m³·mol^-1	ChemAxon
Polarizability	36.57 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.9911
Blood Brain Barrier	+	0.9633
Caco-2 permeable	+	0.8866
P-glycoprotein substrate	Non-substrate	0.5389
P-glycoprotein inhibitor I	Non-inhibitor	0.6485
P-glycoprotein inhibitor II	Non-inhibitor	0.8005
Renal organic cation transporter	Non-inhibitor	0.7229
CYP450 2C9 substrate	Non-substrate	0.796
CYP450 2D6 substrate	Substrate	0.8918
CYP450 3A4 substrate	Substrate	0.6263
CYP450 1A2 substrate	Inhibitor	0.9107
CYP450 2C9 inhibitor	Non-inhibitor	0.9071
CYP450 2D6 inhibitor	Inhibitor	0.8448
CYP450 2C19 inhibitor	Inhibitor	0.778
CYP450 3A4 inhibitor	Inhibitor	0.7959
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.8558
Ames test	Non AMES toxic	0.689
Carcinogenicity	Non-carcinogens	0.9503
Biodegradation	Not ready biodegradable	0.9262
Rat acute toxicity	2.9877 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9329
hERG inhibition (predictor II)	Non-inhibitor	0.7274

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
GC-MS Spectrum - EI-B	GC-MS	splash10-0079-4569000000-42d74df972bf1280fb29
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0006-0009000000-376bdab66f9ada8143f2
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0f6x-0049000000-fbf8945b1b40a8e629ff
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-00di-0779000000-37837168aff5cb2db6db
MS/MS Spectrum - , positive	LC-MS/MS	splash10-0006-0019000000-175d5d7601656bade9be
MS/MS Spectrum - , positive	LC-MS/MS	splash10-00dl-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

Details1. cAMP-specific 3',5'-cyclic phosphodiesterase 4B

Kind: Protein
Organism: Humans
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

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]
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]
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]
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]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	17	N/A	N/A	21087867
IC 50 (nM)	21	N/A	N/A	21705115
IC 50 (nM)	210	N/A	N/A	21602043
IC 50 (nM)	36	N/A	N/A	22321214
IC 50 (nM)	39.81	N/A	N/A	19883461
IC 50 (nM)	40	N/A	N/A	22834877
IC 50 (nM)	56.9	N/A	N/A	20450197
IC 50 (nM)	76	N/A	N/A	20450197

Details2. cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A

Kind: Protein
Organism: Humans
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

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 April 21, 2019 05:50

Papaverine

Identification

Structure for Papaverine (DB01113)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References