ROLIPRAM

Details

Stereochemistry	RACEMIC
Molecular Formula	C16H21NO3
Molecular Weight	275.3428
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(OC2CCCC2)C=C(C=C1)C3CNC(=O)C3

InChI

InChIKey=HJORMJIFDVBMOB-UHFFFAOYSA-N

InChI=1S/C16H21NO3/c1-19-14-7-6-11(12-9-16(18)17-10-12)8-15(14)20-13-4-2-3-5-13/h6-8,12-13H,2-5,9-10H2,1H3,(H,17,18)

HIDE SMILES / InChI

Molecular Formula	C16H21NO3
Molecular Weight	275.3428
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.depression-guide.com/rolipram.htm
Curator's Comment: description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00011375 | https://www.ncbi.nlm.nih.gov/pubmed/19776093 | https://www.ncbi.nlm.nih.gov/pubmed/1475038 | https://www.ncbi.nlm.nih.gov/pubmed/28202289

Rolipram is a selective phosphodiesterase-4 inhibitor discovered and developed by Schering AG as a potential antidepressant drug in the early 1990s. Rolipram was discontinued after clinical trials showed that its therapeutic window was too narrow. Rolipram could not be dosed at high enough levels to be effective without causing significant gastrointestinal side effects. Rolipram promotes apoptosis in HL60 cells through a cAMP-independent mechanism and has been shown to enhance neuronal survival.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Phosphodiesterase 4A 13 Target ID: CHEMBL254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11052785	Inhibitor 8504	4.0 nM [IC50]
Phosphodiesterase 4B 11 Target ID: CHEMBL275 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18686943	Inhibitor 8504	20.0 nM [IC50]
Phosphodiesterase 4D 14 Target ID: CHEMBL288 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16263279	Inhibitor 8504	33.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Multiple sclerosis 107 Sources: https://clinicaltrials.gov/ct2/show/NCT00011375	Primary	Phase II 1147	Unknown Approved Use Unknown
Huntington's disease 28 Sources: https://clinicaltrials.gov/ct2/show/NCT01602900	Primary	Phase I 438	Unknown Approved Use Unknown
Major depressive disorder 179 Sources: https://clinicaltrials.gov/ct2/show/NCT00369798	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1.21 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2095571/	12.5 mg single, topical dose: 12.5 mg route of administration: Topical experiment type: SINGLE co-administered:	ROLIPRAM, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2328751/	0.1 mg single, intravenous dose: 0.1 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ROLIPRAM, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2328751/	0.1 mg single, intravenous dose: 0.1 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ROLIPRAM, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
15.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2328751/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ROLIPRAM, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
16.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2328751/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ROLIPRAM, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
18.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2095571/	12.5 mg single, topical dose: 12.5 mg route of administration: Topical experiment type: SINGLE co-administered:	ROLIPRAM, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4.24 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2328751/	0.1 mg single, intravenous dose: 0.1 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ROLIPRAM, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.27 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2328751/	0.1 mg single, intravenous dose: 0.1 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ROLIPRAM, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
29.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2328751/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ROLIPRAM, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
28.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2328751/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ROLIPRAM, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
3.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2095571/	12.5 mg single, topical dose: 12.5 mg route of administration: Topical experiment type: SINGLE co-administered:	ROLIPRAM, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2328751/	0.1 mg single, intravenous dose: 0.1 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ROLIPRAM, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2328751/	0.1 mg single, intravenous dose: 0.1 mg route of administration: Intravenous experiment type: SINGLE co-administered:	ROLIPRAM, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2328751/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ROLIPRAM, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2328751/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ROLIPRAM, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
4% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12458404/			ROLIPRAM, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
3 mg 3 times / day multiple, oral Highest studied dose Dose: 3 mg, 3 times / day Route: oral Route: multiple Dose: 3 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/	Disc. AE: Headache, Fatigue... AEs leading to discontinuation/dose reduction: Headache (16.7%) Fatigue (16.7%) Hypersensitivity (16.7%) Insomnia (grade 3, 16.7%) Gastroesophageal reflux (16.7%) Balance disorder (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/
1 mg 3 times / day multiple, oral Studied dose Dose: 1 mg, 3 times / day Route: oral Route: multiple Dose: 1 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1475038/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1475038/	Sources: https://pubmed.ncbi.nlm.nih.gov/1475038/

AEs

AE	Significance	Dose	Population
Balance disorder	16.7% Disc. AE	3 mg 3 times / day multiple, oral Highest studied dose Dose: 3 mg, 3 times / day Route: oral Route: multiple Dose: 3 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/
Fatigue	16.7% Disc. AE	3 mg 3 times / day multiple, oral Highest studied dose Dose: 3 mg, 3 times / day Route: oral Route: multiple Dose: 3 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/
Gastroesophageal reflux	16.7% Disc. AE	3 mg 3 times / day multiple, oral Highest studied dose Dose: 3 mg, 3 times / day Route: oral Route: multiple Dose: 3 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/
Headache	16.7% Disc. AE	3 mg 3 times / day multiple, oral Highest studied dose Dose: 3 mg, 3 times / day Route: oral Route: multiple Dose: 3 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/
Hypersensitivity	16.7% Disc. AE	3 mg 3 times / day multiple, oral Highest studied dose Dose: 3 mg, 3 times / day Route: oral Route: multiple Dose: 3 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/
Insomnia	grade 3, 16.7% Disc. AE	3 mg 3 times / day multiple, oral Highest studied dose Dose: 3 mg, 3 times / day Route: oral Route: multiple Dose: 3 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19776093/

PubMed

Title	Date	PubMed
Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network.	2014-04-25	24771768
Flavanoids induce expression of the suppressor of cytokine signalling 3 (SOCS3) gene and suppress IL-6-activated signal transducer and activator of transcription 3 (STAT3) activation in vascular endothelial cells.	2013-09-01	23782265
Anti-inflammatory properties of Septilin in lipopolysaccharide activated monocytes and macrophage.	2011-03	20384571
Phosphodiesterase isozymes involved in regulating acid secretion in the isolated mouse stomach.	2009-12	20388963
Regulation of AMP-activated protein kinase by cAMP in adipocytes: roles for phosphodiesterases, protein kinase B, protein kinase A, Epac and lipolysis.	2009-05	19167487
Rolipram, a specific type-4 phosphodiesterase inhibitor, inhibits cyclophosphamide-induced haemorrhagic cystitis in rats.	2009-01	18710439
Prophylactic effect of irsogladine maleate against indomethacin-induced small intestinal lesions in rats.	2008-10	18306037
Effect of phosphodiesterase type 4 inhibitor rolipram on cyclophosphamide-induced cystitis in rats.	2008-05-31	18358472
Investigation of the alkenyldiarylmethane non-nucleoside reverse transcriptase inhibitors as potential cAMP phosphodiesterase-4B2 inhibitors.	2008-02-15	18222088
Phosphodiesterase-4 blunts inotropism and arrhythmias but not sinoatrial tachycardia of (-)-adrenaline mediated through mouse cardiac beta(1)-adrenoceptors.	2008-02	18084319
Effects of phosphodiesterase 4 inhibition on alveolarization and hyperoxia toxicity in newborn rats.	2008	18941502
The role of IFN-gamma in regulation of IFN-gamma-inducible protein 10 (IP-10) expression in lung epithelial cell and peripheral blood mononuclear cell co-cultures.	2007-11-08	17996064
Neuronal and smooth muscle receptors involved in the PACAP- and VIP-induced relaxations of the pig urinary bladder neck.	2006-09	16847435
ANP-mediated cGMP signaling and phosphodiesterase inhibition in the rat cervical spinal cord.	2006-06	16621444
Effect of orally administered rolipram, a phosphodiesterase 4 inhibitor, on a mouse model of the dermatitis caused by 2,4,6-trinitro-1-chlorobenzene (TNCB)-repeated application.	2006-02-17	16442096
Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation.	2005-08-08	16083514
Phosphodiesterase 4D forms a cAMP diffusion barrier at the apical membrane of the airway epithelium.	2005-03-04	15611099
A2A adenosine receptor induction inhibits IFN-gamma production in murine CD4+ T cells.	2005-01-15	15634932
The epidermal growth factor-like growth factor amphiregulin is strongly induced by the adenosine 3',5'-monophosphate pathway in various cell types.	2004-11	15284208
Endothelins induce ETB receptor-mediated mechanical hypernociception in rat hindpaw: roles of cAMP and protein kinase C.	2004-10-06	15464066
Protection against doxorubicin cardiomyopathy in rats: role of phosphodiesterase inhibitors type 4.	2004-06	15231041
[Rolipram, a specific type IV phosphodiesterase inhibitor, ameliorates indomethacin-induced gastric mucosal injury in rats].	2004-03	15038085
Adenosine receptors and phosphodiesterase inhibitors stimulate Cl- secretion in Calu-3 cells.	2003-09	12714375
Attenuation of the activity of the cAMP-specific phosphodiesterase PDE4A5 by interaction with the immunophilin XAP2.	2003-08-29	12810716
Rolipram, a specific type IV phosphodiesterase inhibitor, ameliorates indomethacin-induced gastric mucosal injury in rats.	2003-05	14567935
DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer.	2002-06	12070754
Endotoxin potentiation of trichothecene-induced lymphocyte apoptosis is mediated by up-regulation of glucocorticoids.	2002-04-01	11922776
The phosphodiesterase inhibitors pentoxifylline and rolipram suppress macrophage activation and nitric oxide production in vitro and in vivo.	2001-02	11161985
Effects of several glucocorticosteroids and PDE4 inhibitors on increases in total lung eosinophil peroxidase (EPO) levels following either systemic or intratracheal administration in sephadex- or ovalbumin-induced inflammatory models.	2000-08	10850854
Use of an activation-specific probe to show that Rap1A and Rap1B display different sensitivities to activation by forskolin in rat1 cells.	2000-07-21	10908723
beta-Adrenoceptor stimulation up-regulates phosphodiesterase 4 activity and reduces prostaglandin E2-inhibitory effects in human neutrophils.	2000-04	10763856
Pharmacological modulation of secondary mediator systems--cyclic AMP and cyclic GMP--on inflammatory hyperalgesia.	1999-06	10401557
The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform.	1999-05-21	10329691
Exogenous and endogenous catecholamines inhibit the production of macrophage inflammatory protein (MIP) 1 alpha via a beta adrenoceptor mediated mechanism.	1998-11	9863660
Phosphodiesterase type 4 inhibitors, but not glucocorticoids, are more potent in suppression of cytokine secretion by mononuclear cells from atopic than nonatopic donors.	1998-11	9819297
Inhibition of phosphodiesterase type IV suppresses human immunodeficiency virus type 1 replication and cytokine production in primary T cells: involvement of NF-kappaB and NFAT.	1998-06	9573235
Expression, purification, and characterization of human cAMP-specific phosphodiesterase (PDE4) subtypes A, B, C, and D.	1997-05-19	9177268
The effect of selective phosphodiesterase 3 and 4 isoenzyme inhibitors and established anti-asthma drugs on inflammatory cell activation.	1996-11	8937731
Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus.	1996-04-01	8601816
Delayed sympathectomy after a prolonged hyperalgesia results in a subsequent enhanced acute hyperalgesic response.	1996-04	8684612
Action of cAMP on expression and release of adhesion molecules in human endothelial cells.	1996-03	8780174
Dipyridamole enhances interleukin-1beta-stimulated nitric oxide production by cultured rat vascular smooth muscle cells.	1996-02-05	8904084
Rolipram, a specific type IV phosphodiesterase inhibitor, is a potent inhibitor of HIV-1 replication.	1995-10	8519449
Multiple second messenger systems act sequentially to mediate rolipram-induced prolongation of prostaglandin E2-induced mechanical hyperalgesia in the rat.	1995-02	7715785
Studies on anti-allergic action of AH 21-132, a novel isozyme-selective phosphodiesterase inhibitor in airways.	1995-02	7542355
Further confirmation of the role of adenyl cyclase and of cAMP-dependent protein kinase in primary afferent hyperalgesia.	1991	1722888

Patents

Sample Use Guides

In Vivo Use Guide

Rolipram in Stage I were dosed up to 9 mg/day (3 mg, three times daily), patients in Stage II were dosed only up to 7.5 mg/day

Route of Administration: Oral

In Vitro Use Guide

The Glioblastoma cancer stem-like cells isolated from T2 at 5th passages having a purity of >95% based on the assessment of CD133 and CD15 expressions were harvested and seeded in 24-well plates containing DMEM-F12 at a density of 2.5 × 104 cells/well, overnight. The cells were treated with various concentrations (1, 3, 10, 30, 100 μg/ml) of bevacizumab (Roche, Switzerland) for 48 h. All treatments were done in quadruplicate. After finding of half maximal inhibitory concentration (IC50) of bevacizumab, the cells incubated with bevacizumab at IC50 in the absence or presence of rolipram (103 μM).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:00:29 GMT 2025` Edited by `admin` on `Mon Mar 31 18:00:29 GMT 2025`
Record UNII	K676NL63N7
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SB-95952

Preferred Name

English

ROLIPRAM

Official Name

English

ROLIPRAM [MI]

Common Name

English

(±)-ROLIPRAM

Common Name

English

Rolipram [WHO-DD]

Common Name

English

ZK-62771

Code

English

(R,S)-ROLIPRAM

Common Name

English

4-(3-CYCLOPENTYLOXY-4-METHOXYPHENYL)PYRROLIDONE

Systematic Name

English

ZK 62 711

Code

English

ROLIPRAM [JAN]

Common Name

English

ROLIPRAM [MART.]

Common Name

English

ZK-62711

Code

English

ROLIPRAM [USAN]

Common Name

English

NSC-760125

Code

English

rolipram [INN]

Common Name

English

4-[3-(Cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidinone

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C257