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Details

Stereochemistry ACHIRAL
Molecular Formula C20H21NO4
Molecular Weight 339.385
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PAPAVERINE

SMILES

COC1=C(OC)C=C(CC2=NC=CC3=CC(OC)=C(OC)C=C23)C=C1

InChI

InChIKey=XQYZDYMELSJDRZ-UHFFFAOYSA-N
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

HIDE SMILES / InChI
An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. Papaverine is a vasodilating agent. Papaverine is used for the treating certain conditions that are accompanied by smooth muscle spasms (eg, blood vessel, urinary, gallbladder, or intestinal spasm). 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. Papaverine is a potent, specific inhibitor of PDE10A. Papaverine for treatment of erectile dysfunction (ED) is excluded from coverage.

CNS Activity

Curator's Comment: CNS active in animal models, but it is practically devoid of effects on the central nervous system in humans. When administered chronically to mice, Papaverine produced motor and cognitive deficits and increased anxiety, but conversely could produce an antipsychotic effect.

Originator

Curator's Comment: Papaverine is a benzylisoquinoline alkaloid that was discovered by Merck (1848) as a minor (ca. 1%) component in the latex of the opium poppy (Papaver somniferum L.). # Merck

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Papaverine

Approved Use

Papaverine is recommended in various conditions accompanied by spasm of smooth muscle, such as vascular spasm associated with acute myocardial infarction (coronary occlusion), angina pectoris, peripheral and pulmonary embolism, peripheral vascular disease in which there is a vasospastic element, or certain cerebral angiospastic states; and visceral spasm, as in ureteral, biliary, or gastrointestinal colic.
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
54.7 ng/mL
3 mg single, intravascular
dose: 3 mg
route of administration: Intravascular
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
583 ng/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
117 ng/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
536 ng/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
218 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1760 mg × h/mL
80 mg single, intravenous
dose: 80 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
375 mg × h/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
1965 mg × h/mL
80 mg single, intravenous
dose: 80 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
855 mg × h/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1308 ng × h/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
409 ng × h/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1247 ng × h/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
800 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.9 h
80 mg single, intravenous
dose: 80 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3.4 h
80 mg single, intravenous
dose: 80 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PAPAVERINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
500 mg 3 times / day multiple, oral
Higher than recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: multiple
Dose: 500 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Disc. AE: Alkaline phosphatase increased, SGOT increased...
AEs leading to
discontinuation/dose reduction:
Alkaline phosphatase increased (4%)
SGOT increased (4%)
Eosinophilia (4%)
Sources:
15 g single, oral
Overdose
Dose: 15 g
Route: oral
Route: single
Dose: 15 g
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
Disc. AE: Consciousness decreased, Respiration abnormal...
AEs leading to
discontinuation/dose reduction:
Consciousness decreased
Respiration abnormal
Metabolic acidosis
Respiratory alkalosis
Sinus tachycardia
Hypokalemia (grade 2)
Hyperglycemia (grade 1)
Pyruvate increased
Sources:
8 g single, oral
Overdose
Dose: 8 g
Route: oral
Route: single
Dose: 8 g
Sources:
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Sources:
Disc. AE: Lactic acidosis, Hypokalemia...
AEs leading to
discontinuation/dose reduction:
Lactic acidosis (grade 3)
Hypokalemia
Coma (grade 5)
Convulsions (grade 3)
Vomiting (grade 3)
Respiratory alkalosis (grade 5)
Sources:
AEs

AEs

AESignificanceDosePopulation
Alkaline phosphatase increased 4%
Disc. AE
500 mg 3 times / day multiple, oral
Higher than recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: multiple
Dose: 500 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Eosinophilia 4%
Disc. AE
500 mg 3 times / day multiple, oral
Higher than recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: multiple
Dose: 500 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
SGOT increased 4%
Disc. AE
500 mg 3 times / day multiple, oral
Higher than recommended
Dose: 500 mg, 3 times / day
Route: oral
Route: multiple
Dose: 500 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Consciousness decreased Disc. AE
15 g single, oral
Overdose
Dose: 15 g
Route: oral
Route: single
Dose: 15 g
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
Metabolic acidosis Disc. AE
15 g single, oral
Overdose
Dose: 15 g
Route: oral
Route: single
Dose: 15 g
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
Pyruvate increased Disc. AE
15 g single, oral
Overdose
Dose: 15 g
Route: oral
Route: single
Dose: 15 g
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
Respiration abnormal Disc. AE
15 g single, oral
Overdose
Dose: 15 g
Route: oral
Route: single
Dose: 15 g
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
Respiratory alkalosis Disc. AE
15 g single, oral
Overdose
Dose: 15 g
Route: oral
Route: single
Dose: 15 g
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
Sinus tachycardia Disc. AE
15 g single, oral
Overdose
Dose: 15 g
Route: oral
Route: single
Dose: 15 g
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
Hyperglycemia grade 1
Disc. AE
15 g single, oral
Overdose
Dose: 15 g
Route: oral
Route: single
Dose: 15 g
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
Hypokalemia grade 2
Disc. AE
15 g single, oral
Overdose
Dose: 15 g
Route: oral
Route: single
Dose: 15 g
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
Hypokalemia Disc. AE
8 g single, oral
Overdose
Dose: 8 g
Route: oral
Route: single
Dose: 8 g
Sources:
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Sources:
Convulsions grade 3
Disc. AE
8 g single, oral
Overdose
Dose: 8 g
Route: oral
Route: single
Dose: 8 g
Sources:
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Sources:
Lactic acidosis grade 3
Disc. AE
8 g single, oral
Overdose
Dose: 8 g
Route: oral
Route: single
Dose: 8 g
Sources:
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Sources:
Vomiting grade 3
Disc. AE
8 g single, oral
Overdose
Dose: 8 g
Route: oral
Route: single
Dose: 8 g
Sources:
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Sources:
Coma grade 5
Disc. AE
8 g single, oral
Overdose
Dose: 8 g
Route: oral
Route: single
Dose: 8 g
Sources:
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Sources:
Respiratory alkalosis grade 5
Disc. AE
8 g single, oral
Overdose
Dose: 8 g
Route: oral
Route: single
Dose: 8 g
Sources:
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Sources:
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive [IC50 >10 uM]
inconclusive [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
weak [Inhibition 100 uM]
yes [IC50 0.762 uM]
yes [IC50 1.9953 uM]
yes [IC50 12.5893 uM]
yes [IC50 23.13 uM]
yes [IC50 <10 uM]
yes [Inhibition 10 uM]
yes [Inhibition 10 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
Tox targets
PubMed

PubMed

TitleDatePubMed
Papaverine-induced chronic liver disease.
1986 Apr
Maintenance treatment of erectile impotence by cavernosal unstriated muscle relaxant injection.
1986 Aug
Incompatibility of Hexabrix and papaverine in peripheral arteriography.
1987 Mar
Pressor inhibition of angiotensin-induced ACTH secretion.
1987 Nov
Diagnosis of male impotence after intracavernous papaverine test.
1988
[Efficacy of vascular therapy in complex of treatment of purulent necrotic foot ulcers in patients with diabetes mellitus].
2001 Feb
Papaverine blocks hKv1.5 channel current and human atrial ultrarapid delayed rectifier K+ currents.
2003 Feb
Adenosine receptors and phosphodiesterase inhibitors stimulate Cl- secretion in Calu-3 cells.
2003 Sep
[X-ray densitometric measurement of myocardial perfusion reserve in symptomatic patients without angiographically detectable coronary stenoses].
2008 Apr
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.
2008 Dec
Insulin resistance functionally limits endothelium-dependent coronary vasodilation in nondiabetic patients.
2008 Jan
Adverse effects of topical papaverine on auditory nerve function.
2008 Sep
Abnormal responses of the human cerebral microcirculation to papaverin during aneurysm surgery.
2009 Jan
Patents

Sample Use Guides

Papaverine Hydrochloride may be administered intravenously or intramuscularly. The intravenous route is recommended when an immediate effect is desired, but the drug must be injected slowly over the course of 1 or 2 minutes to avoid uncomfortable or alarming side effects. Parenteral administration of papaverine hydrochloride in doses of 1 to 4 mL is repeated every 3 hours as indicated. In the treatment of cardiac extrasystoles, 2 doses may be given 10 minutes apart.
Route of Administration: Parenteral
In bovine cauda epididymal and ejaculated spermatozoa, the major cAMP-PDE activity was papaverine-sensitive (44.5% and 57.5%, respectively, at 400 nm of papaverine).
Name Type Language
PAPAVERINUM
HPUS  
Preferred Name English
PAPAVERINE
MART.   MI   VANDF   WHO-DD  
Common Name English
PAPAVERINE [MART.]
Common Name English
PAPAVERINUM [HPUS]
Common Name English
NSC-136630
Code English
6,7-DIMETHOXY-1-VERATRYLISOQUINOLINE
Systematic Name English
ISOQUINOLINE, 1-((3,4-DIMETHOXYPHENYL)METHYL)-6,7-DIMETHOXY-
Systematic Name English
NOSCAPINE IMPURITY A [EP IMPURITY]
Common Name English
PAPAVERINE [MI]
Common Name English
Papaverine [WHO-DD]
Common Name English
PAPAVERINE [VANDF]
Common Name English
Classification Tree Code System Code
WHO-VATC QG04BE02
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
WHO-ATC G04BE52
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
FDA ORPHAN DRUG 64991
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
NCI_THESAURUS C29707
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
FDA ORPHAN DRUG 581417
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
WHO-ATC G04BE02
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
WHO-VATC QA03AD01
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
WHO-VATC QG04BE52
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
LIVERTOX 739
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
WHO-ATC A03AD01
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
NCI_THESAURUS C744
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
Code System Code Type Description
RXCUI
7895
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY RxNorm
WIKIPEDIA
PAPAVERINE
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
NCI_THESAURUS
C726
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
DRUG CENTRAL
2056
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
DRUG BANK
DB01113
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
CAS
58-74-2
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
DAILYMED
DAA13NKG2Q
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
MESH
D010208
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
PUBCHEM
4680
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
HSDB
3147
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
ECHA (EC/EINECS)
200-397-2
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
EVMPD
SUB14760MIG
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
EPA CompTox
DTXSID4023418
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
ChEMBL
CHEMBL19224
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
FDA UNII
DAA13NKG2Q
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
SMS_ID
100000079721
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY
MERCK INDEX
m8392
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY Merck Index
NSC
136630
Created by admin on Mon Mar 31 17:54:24 GMT 2025 , Edited by admin on Mon Mar 31 17:54:24 GMT 2025
PRIMARY