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Details

Stereochemistry ABSOLUTE
Molecular Formula 2C14H14O3.C4H10N2
Molecular Weight 546.6539
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NAPROXEN PIPERAZINE

SMILES

C1CNCCN1.COC2=CC3=CC=C(C=C3C=C2)[C@H](C)C(O)=O.COC4=CC5=CC=C(C=C5C=C4)[C@H](C)C(O)=O

InChI

InChIKey=KRDCGZGYWRCHNN-NAWJVIAPSA-N
InChI=1S/2C14H14O3.C4H10N2/c2*1-9(14(15)16)10-3-4-12-8-13(17-2)6-5-11(12)7-10;1-2-6-4-3-5-1/h2*3-9H,1-2H3,(H,15,16);5-6H,1-4H2/t2*9-;/m00./s1

HIDE SMILES / InChI

Molecular Formula C14H14O3
Molecular Weight 230.2592
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula C4H10N2
Molecular Weight 86.1356
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/68009288

Naproxen (naproxen sodium, NAPROSYN®) is a propionic acid derivative related to the arylacetic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). It is an anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. The mechanism of action of the naproxen (naproxen sodium, NAPROSYN®), like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).

CNS Activity

Curator's Comment: Naproxen is a potent inhibitor of prostaglandin synthesis in vitro. Naproxen concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models.

Originator

Curator's Comment: Syntex was integrated into the Roche group in 1994.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NAPROSYN

Approved Use

NAPROSYN is indicated: For the relief of the signs and symptoms of rheumatoid arthritis. For the relief of the signs and symptoms of osteoarthritis. For the relief of the signs and symptoms of ankylosing spondylitis. For the relief of the signs and symptoms of juvenile arthritis. NAPROSYN is also indicated: For relief of the signs and symptoms of tendonitis. For relief of the signs and symptoms of bursitis. For relief of the signs and symptoms of acute gout. For the management of pain. For the management of primary dysmenorrhea.

Launch Date

1.95350397E11
Primary
NAPROSYN

Approved Use

NAPROSYN is indicated: For the relief of the signs and symptoms of rheumatoid arthritis. For the relief of the signs and symptoms of osteoarthritis. For the relief of the signs and symptoms of ankylosing spondylitis. For the relief of the signs and symptoms of juvenile arthritis. NAPROSYN is also indicated: For relief of the signs and symptoms of tendonitis. For relief of the signs and symptoms of bursitis. For relief of the signs and symptoms of acute gout. For the management of pain. For the management of primary dysmenorrhea.

Launch Date

1.95350397E11
Primary
NAPROSYN

Approved Use

NAPROSYN is indicated: For the relief of the signs and symptoms of rheumatoid arthritis. For the relief of the signs and symptoms of osteoarthritis. For the relief of the signs and symptoms of ankylosing spondylitis. For the relief of the signs and symptoms of juvenile arthritis. NAPROSYN is also indicated: For relief of the signs and symptoms of tendonitis. For relief of the signs and symptoms of bursitis. For relief of the signs and symptoms of acute gout. For the management of pain. For the management of primary dysmenorrhea.

Launch Date

1.95350397E11
Primary
NAPROSYN

Approved Use

NAPROSYN is indicated: For the relief of the signs and symptoms of rheumatoid arthritis. For the relief of the signs and symptoms of osteoarthritis. For the relief of the signs and symptoms of ankylosing spondylitis. For the relief of the signs and symptoms of juvenile arthritis. NAPROSYN is also indicated: For relief of the signs and symptoms of tendonitis. For relief of the signs and symptoms of bursitis. For relief of the signs and symptoms of acute gout. For the management of pain. For the management of primary dysmenorrhea.

Launch Date

1.95350397E11
Primary
NAPROSYN

Approved Use

NAPROSYN is indicated: For the relief of the signs and symptoms of rheumatoid arthritis. For the relief of the signs and symptoms of osteoarthritis. For the relief of the signs and symptoms of ankylosing spondylitis. For the relief of the signs and symptoms of juvenile arthritis. NAPROSYN is also indicated: For relief of the signs and symptoms of tendonitis. For relief of the signs and symptoms of bursitis. For relief of the signs and symptoms of acute gout. For the management of pain. For the management of primary dysmenorrhea.

Launch Date

1.95350397E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
95 μg/L
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NAPROXEN plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
94 μg/mL
1000 mg 1 times / day steady-state, oral
dose: 1000 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NAPROXEN plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1446 μg × h/mL
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NAPROXEN plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1448 μg × h/mL
1000 mg 1 times / day steady-state, oral
dose: 1000 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NAPROXEN plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
15 h
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NAPROXEN plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NAPROXEN plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
12.5 g single, oral
Overdose
Dose: 12.5 g
Route: oral
Route: single
Dose: 12.5 g
Sources: Page: 1102/129
healthy, 15
n = 1
Health Status: healthy
Age Group: 15
Sex: F
Population Size: 1
Sources: Page: 1102/129
Disc. AE: Abdominal pain, Nausea...
AEs leading to
discontinuation/dose reduction:
Abdominal pain
Nausea
Dizziness
Seizures
Metabolic acidosis (severe)
Sources: Page: 1102/129
4 g single, oral
Highest studied dose
Dose: 4 g
Route: oral
Route: single
Dose: 4 g
Sources: Page: p.272
healthy, 20
n = 4
Health Status: healthy
Age Group: 20
Sex: M
Population Size: 4
Sources: Page: p.272
70.4 g single, oral
Overdose
Dose: 70.4 g
Route: oral
Route: single
Dose: 70.4 g
Co-administed with::
alcohol, p.o
Sources: Page: p.103
healthy, 28
n = 1
Health Status: healthy
Age Group: 28
Sex: M
Population Size: 1
Sources: Page: p.103
Disc. AE: Sinus tachycardia, Drowsiness...
AEs leading to
discontinuation/dose reduction:
Sinus tachycardia
Drowsiness
Metabolic acidosis
Seizures
Sources: Page: p.103
26 g single, oral
Overdose
Dose: 26 g
Route: oral
Route: single
Dose: 26 g
Sources: Page: p.458
unhealthy, 58
n = 1
Health Status: unhealthy
Condition: Depressive syndrome|Anxiety
Age Group: 58
Sex: F
Population Size: 1
Sources: Page: p.458
Disc. AE: Thrombopenia...
AEs leading to
discontinuation/dose reduction:
Thrombopenia
Sources: Page: p.458
550 mg 2 times / day multiple, oral
Recommended
Dose: 550 mg, 2 times / day
Route: oral
Route: multiple
Dose: 550 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain|Primary Dysmenorrhea| Acute Tendonitis| Acute Bursitis
Sources: Page: p.1
Disc. AE: Cardiac thrombosis, Myocardial infarction...
AEs leading to
discontinuation/dose reduction:
Cardiac thrombosis (grade 3-5)
Myocardial infarction (grade 3-5)
Stroke (grade 3-5)
Gastrointestinal disorder NOS (grade 3-5)
Gastrointestinal bleeding (grade 3-5)
Gastrointestinal ulcer (grade 3-5)
Perforation stomach (grade 3-5)
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Abdominal pain Disc. AE
12.5 g single, oral
Overdose
Dose: 12.5 g
Route: oral
Route: single
Dose: 12.5 g
Sources: Page: 1102/129
healthy, 15
n = 1
Health Status: healthy
Age Group: 15
Sex: F
Population Size: 1
Sources: Page: 1102/129
Dizziness Disc. AE
12.5 g single, oral
Overdose
Dose: 12.5 g
Route: oral
Route: single
Dose: 12.5 g
Sources: Page: 1102/129
healthy, 15
n = 1
Health Status: healthy
Age Group: 15
Sex: F
Population Size: 1
Sources: Page: 1102/129
Nausea Disc. AE
12.5 g single, oral
Overdose
Dose: 12.5 g
Route: oral
Route: single
Dose: 12.5 g
Sources: Page: 1102/129
healthy, 15
n = 1
Health Status: healthy
Age Group: 15
Sex: F
Population Size: 1
Sources: Page: 1102/129
Seizures Disc. AE
12.5 g single, oral
Overdose
Dose: 12.5 g
Route: oral
Route: single
Dose: 12.5 g
Sources: Page: 1102/129
healthy, 15
n = 1
Health Status: healthy
Age Group: 15
Sex: F
Population Size: 1
Sources: Page: 1102/129
Metabolic acidosis severe
Disc. AE
12.5 g single, oral
Overdose
Dose: 12.5 g
Route: oral
Route: single
Dose: 12.5 g
Sources: Page: 1102/129
healthy, 15
n = 1
Health Status: healthy
Age Group: 15
Sex: F
Population Size: 1
Sources: Page: 1102/129
Drowsiness Disc. AE
70.4 g single, oral
Overdose
Dose: 70.4 g
Route: oral
Route: single
Dose: 70.4 g
Co-administed with::
alcohol, p.o
Sources: Page: p.103
healthy, 28
n = 1
Health Status: healthy
Age Group: 28
Sex: M
Population Size: 1
Sources: Page: p.103
Metabolic acidosis Disc. AE
70.4 g single, oral
Overdose
Dose: 70.4 g
Route: oral
Route: single
Dose: 70.4 g
Co-administed with::
alcohol, p.o
Sources: Page: p.103
healthy, 28
n = 1
Health Status: healthy
Age Group: 28
Sex: M
Population Size: 1
Sources: Page: p.103
Seizures Disc. AE
70.4 g single, oral
Overdose
Dose: 70.4 g
Route: oral
Route: single
Dose: 70.4 g
Co-administed with::
alcohol, p.o
Sources: Page: p.103
healthy, 28
n = 1
Health Status: healthy
Age Group: 28
Sex: M
Population Size: 1
Sources: Page: p.103
Sinus tachycardia Disc. AE
70.4 g single, oral
Overdose
Dose: 70.4 g
Route: oral
Route: single
Dose: 70.4 g
Co-administed with::
alcohol, p.o
Sources: Page: p.103
healthy, 28
n = 1
Health Status: healthy
Age Group: 28
Sex: M
Population Size: 1
Sources: Page: p.103
Thrombopenia Disc. AE
26 g single, oral
Overdose
Dose: 26 g
Route: oral
Route: single
Dose: 26 g
Sources: Page: p.458
unhealthy, 58
n = 1
Health Status: unhealthy
Condition: Depressive syndrome|Anxiety
Age Group: 58
Sex: F
Population Size: 1
Sources: Page: p.458
Cardiac thrombosis grade 3-5
Disc. AE
550 mg 2 times / day multiple, oral
Recommended
Dose: 550 mg, 2 times / day
Route: oral
Route: multiple
Dose: 550 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain|Primary Dysmenorrhea| Acute Tendonitis| Acute Bursitis
Sources: Page: p.1
Gastrointestinal bleeding grade 3-5
Disc. AE
550 mg 2 times / day multiple, oral
Recommended
Dose: 550 mg, 2 times / day
Route: oral
Route: multiple
Dose: 550 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain|Primary Dysmenorrhea| Acute Tendonitis| Acute Bursitis
Sources: Page: p.1
Gastrointestinal disorder NOS grade 3-5
Disc. AE
550 mg 2 times / day multiple, oral
Recommended
Dose: 550 mg, 2 times / day
Route: oral
Route: multiple
Dose: 550 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain|Primary Dysmenorrhea| Acute Tendonitis| Acute Bursitis
Sources: Page: p.1
Gastrointestinal ulcer grade 3-5
Disc. AE
550 mg 2 times / day multiple, oral
Recommended
Dose: 550 mg, 2 times / day
Route: oral
Route: multiple
Dose: 550 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain|Primary Dysmenorrhea| Acute Tendonitis| Acute Bursitis
Sources: Page: p.1
Myocardial infarction grade 3-5
Disc. AE
550 mg 2 times / day multiple, oral
Recommended
Dose: 550 mg, 2 times / day
Route: oral
Route: multiple
Dose: 550 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain|Primary Dysmenorrhea| Acute Tendonitis| Acute Bursitis
Sources: Page: p.1
Perforation stomach grade 3-5
Disc. AE
550 mg 2 times / day multiple, oral
Recommended
Dose: 550 mg, 2 times / day
Route: oral
Route: multiple
Dose: 550 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain|Primary Dysmenorrhea| Acute Tendonitis| Acute Bursitis
Sources: Page: p.1
Stroke grade 3-5
Disc. AE
550 mg 2 times / day multiple, oral
Recommended
Dose: 550 mg, 2 times / day
Route: oral
Route: multiple
Dose: 550 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain|Primary Dysmenorrhea| Acute Tendonitis| Acute Bursitis
Sources: Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 4.67 uM]
yes [IC50 486 uM]
yes [IC50 5.67 uM]
yes [IC50 85.4 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
Persistent pulmonary hypertension after maternal naproxen ingestion in a term newborn: a case report.
2000
Simultaneous analysis of naproxen, nabumetone and its major metabolite 6-methoxy-2-naphthylacetic acid in pharmaceuticals and human urine by high-performance liquid chromatography.
2000 Oct
Absence of pharmacokinetic interaction between orally co-administered naproxen sodium and diphenhydramine hydrochloride.
2000 Sep
[Two complex suicidal poisonings with drugs and their medicolegal aspects].
2001
Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations.
2001
Risk of ulcer soars with combination of arthritis drugs.
2001 Apr
I'm taking over-the-counter ibuprofen every day for neck pain. Recently, my doctor gave me a prescription for naproxen for my arthritis. Should I be concerned about taking these two together?
2001 Aug
Time and dose dependent augmentation of inhibitory effects of abciximab by aspirin.
2001 Feb
Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2.
2001 Feb
[Drug-induced aphthae].
2001 Jan
Slow-release tramadol for treatment of chronic malignant pain--an open multicenter trial.
2001 Jan
Review article: the gastrointestinal safety profile of rofecoxib, a highly selective inhibitor of cyclooxygenase-2, in humans.
2001 Jan
A possible mechanism of naproxen-induced lipid peroxidation in rat liver microsomes.
2001 Jul
New issues about nitric oxide and its effects on the gastrointestinal tract.
2001 Jul
In vitro evaluation and intra-articular administration of biodegradable microspheres containing naproxen sodium.
2001 Jul-Aug
Fixed drug eruption due to naproxen; lack of cross-reactivity with other propionic acid derivatives.
2001 Jun
Inhibition of tendon cell proliferation and matrix glycosaminoglycan synthesis by non-steroidal anti-inflammatory drugs in vitro.
2001 Jun
High-performance liquid chromatographic method development and validation for the simultaneous quantitation of naproxen sodium and pseudoephedrine hydrochloride impurities.
2001 Mar
Effect of lipophilicity on in vivo iontophoretic delivery. I. NSAIDs.
2001 Mar
Functional status and health-related quality of life of elderly osteoarthritic patients treated with celecoxib.
2001 Mar
Synthesis, in vitro skin permeation studies, and PLS-analysis of new naproxen derivatives.
2001 May
Stereoselective synthesis of (S)-(+)-Naproxen catalyzed by carboxyl esterase in a multicompartment electrolyzer.
2001 May 28
Isotachophoretic determination of naproxen in the presence of its metabolite in human serum.
2001 May 4
Screening procedure for detection of non-steroidal anti-inflammatory drugs and their metabolites in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons by gas chromatography-mass spectrometry after extractive methylation.
2001 May-Jun
Patents

Sample Use Guides

Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis: 1 tablet of NAPROSYN® (250 mg or 375 mg or 500 mg) twice daily. Acute Gout: The recommended starting dose is 750 mg of NAPROSYN® followed by 250 mg every 8 hours until the attack has subsided.
Route of Administration: Oral
There are data on the N-(3-methylpyridin-2-yl)amide derivatives of flurbiprofen and naproxen (Flu-AM1 and Nap-AM1, respectively) with respect to their properties towards fatty acid amide hydrolase (FAAH). Flu-AM1 and Nap-AM1 inhibited FAAH-catalysed hydrolysis of [(3)H]anandamide by rat brain homogenates with IC50 values of 0.44 and 0.74 uM. The corresponding values for flurbiprofen and naproxen were 29 and >100 uM, respectively.
Substance Class Chemical
Created
by admin
on Fri Dec 16 21:22:33 UTC 2022
Edited
by admin
on Fri Dec 16 21:22:33 UTC 2022
Record UNII
R2A8B8HIPI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NAPROXEN PIPERAZINE
WHO-DD  
Common Name English
NAPROXEN PIPERAZINE SALT
MI  
Common Name English
(S)-6-METHOXY-.ALPHA.-METHYLNAPHTHALENE-2-ACETIC ACID, COMPOUND WITH PIPERAZINE (2:1)
Common Name English
NAPROXEN PIPERAZINE SALT [MI]
Common Name English
Naproxen piperazine [WHO-DD]
Common Name English
PIPROXEN
Common Name English
Code System Code Type Description
CAS
70981-66-7
Created by admin on Fri Dec 16 21:22:34 UTC 2022 , Edited by admin on Fri Dec 16 21:22:34 UTC 2022
PRIMARY
PUBCHEM
76968825
Created by admin on Fri Dec 16 21:22:34 UTC 2022 , Edited by admin on Fri Dec 16 21:22:34 UTC 2022
PRIMARY
MERCK INDEX
M7769
Created by admin on Fri Dec 16 21:22:34 UTC 2022 , Edited by admin on Fri Dec 16 21:22:34 UTC 2022
PRIMARY Merck Index
EPA CompTox
DTXSID40221212
Created by admin on Fri Dec 16 21:22:34 UTC 2022 , Edited by admin on Fri Dec 16 21:22:34 UTC 2022
PRIMARY
ECHA (EC/EINECS)
275-083-1
Created by admin on Fri Dec 16 21:22:34 UTC 2022 , Edited by admin on Fri Dec 16 21:22:34 UTC 2022
PRIMARY
FDA UNII
R2A8B8HIPI
Created by admin on Fri Dec 16 21:22:34 UTC 2022 , Edited by admin on Fri Dec 16 21:22:34 UTC 2022
PRIMARY
EVMPD
SUB14897MIG
Created by admin on Fri Dec 16 21:22:34 UTC 2022 , Edited by admin on Fri Dec 16 21:22:34 UTC 2022
PRIMARY
MESH
C504545
Created by admin on Fri Dec 16 21:22:34 UTC 2022 , Edited by admin on Fri Dec 16 21:22:34 UTC 2022
PRIMARY
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PARENT -> SALT/SOLVATE
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ACTIVE MOIETY