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=CC=C(C=C1OC2CCCC2)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 8297	4.0 nM [IC50]
Phosphodiesterase 4B 11 Target ID: CHEMBL275 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18686943	Inhibitor 8297	20.0 nM [IC50]
Phosphodiesterase 4D 14 Target ID: CHEMBL288 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16263279	Inhibitor 8297	33.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Multiple sclerosis 104 Sources: https://clinicaltrials.gov/ct2/show/NCT00011375	Primary	Phase II 1132	Unknown Approved Use Unknown
Huntington's disease 24 Sources: https://clinicaltrials.gov/ct2/show/NCT01602900	Primary	Phase I 428	Unknown Approved Use Unknown
Major depressive disorder 173 Sources: https://clinicaltrials.gov/ct2/show/NCT00369798	Primary	Phase I 428	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
		252159956
Further confirmation of the role of adenyl cyclase and of cAMP-dependent protein kinase in primary afferent hyperalgesia.	1991	1722888
Multiple second messenger systems act sequentially to mediate rolipram-induced prolongation of prostaglandin E2-induced mechanical hyperalgesia in the rat.	1995 Feb	7715785
Studies on anti-allergic action of AH 21-132, a novel isozyme-selective phosphodiesterase inhibitor in airways.	1995 Feb	7542355
Rolipram, a specific type IV phosphodiesterase inhibitor, is a potent inhibitor of HIV-1 replication.	1995 Oct	8519449
Delayed sympathectomy after a prolonged hyperalgesia results in a subsequent enhanced acute hyperalgesic response.	1996 Apr	8684612
Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus.	1996 Apr 1	8601816
Dipyridamole enhances interleukin-1beta-stimulated nitric oxide production by cultured rat vascular smooth muscle cells.	1996 Feb 5	8904084
Action of cAMP on expression and release of adhesion molecules in human endothelial cells.	1996 Mar	8780174
The effect of selective phosphodiesterase 3 and 4 isoenzyme inhibitors and established anti-asthma drugs on inflammatory cell activation.	1996 Nov	8937731
Expression, purification, and characterization of human cAMP-specific phosphodiesterase (PDE4) subtypes A, B, C, and D.	1997 May 19	9177268
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 Jun	9573235
Exogenous and endogenous catecholamines inhibit the production of macrophage inflammatory protein (MIP) 1 alpha via a beta adrenoceptor mediated mechanism.	1998 Nov	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 Nov	9819297
Pharmacological modulation of secondary mediator systems--cyclic AMP and cyclic GMP--on inflammatory hyperalgesia.	1999 Jun	10401557
The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform.	1999 May 21	10329691
beta-Adrenoceptor stimulation up-regulates phosphodiesterase 4 activity and reduces prostaglandin E2-inhibitory effects in human neutrophils.	2000 Apr	10763856
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 Aug	10850854
Use of an activation-specific probe to show that Rap1A and Rap1B display different sensitivities to activation by forskolin in rat1 cells.	2000 Jul 21	10908723
The phosphodiesterase inhibitors pentoxifylline and rolipram suppress macrophage activation and nitric oxide production in vitro and in vivo.	2001 Feb	11161985
Endotoxin potentiation of trichothecene-induced lymphocyte apoptosis is mediated by up-regulation of glucocorticoids.	2002 Apr 1	11922776
DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer.	2002 Jun	12070754
Attenuation of the activity of the cAMP-specific phosphodiesterase PDE4A5 by interaction with the immunophilin XAP2.	2003 Aug 29	12810716
Rolipram, a specific type IV phosphodiesterase inhibitor, ameliorates indomethacin-induced gastric mucosal injury in rats.	2003 May	14567935
Adenosine receptors and phosphodiesterase inhibitors stimulate Cl- secretion in Calu-3 cells.	2003 Sep	12714375
Protection against doxorubicin cardiomyopathy in rats: role of phosphodiesterase inhibitors type 4.	2004 Jun	15231041
[Rolipram, a specific type IV phosphodiesterase inhibitor, ameliorates indomethacin-induced gastric mucosal injury in rats].	2004 Mar	15038085
The epidermal growth factor-like growth factor amphiregulin is strongly induced by the adenosine 3',5'-monophosphate pathway in various cell types.	2004 Nov	15284208
Endothelins induce ETB receptor-mediated mechanical hypernociception in rat hindpaw: roles of cAMP and protein kinase C.	2004 Oct 6	15464066
Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation.	2005 Aug 8	16083514
A2A adenosine receptor induction inhibits IFN-gamma production in murine CD4+ T cells.	2005 Jan 15	15634932
Phosphodiesterase 4D forms a cAMP diffusion barrier at the apical membrane of the airway epithelium.	2005 Mar 4	15611099
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 Feb 17	16442096
ANP-mediated cGMP signaling and phosphodiesterase inhibition in the rat cervical spinal cord.	2006 Jun	16621444
Neuronal and smooth muscle receptors involved in the PACAP- and VIP-induced relaxations of the pig urinary bladder neck.	2006 Sep	16847435
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 Nov 8	17996064
Effects of phosphodiesterase 4 inhibition on alveolarization and hyperoxia toxicity in newborn rats.	2008	18941502
Phosphodiesterase-4 blunts inotropism and arrhythmias but not sinoatrial tachycardia of (-)-adrenaline mediated through mouse cardiac beta(1)-adrenoceptors.	2008 Feb	18084319
Investigation of the alkenyldiarylmethane non-nucleoside reverse transcriptase inhibitors as potential cAMP phosphodiesterase-4B2 inhibitors.	2008 Feb 15	18222088
Effect of phosphodiesterase type 4 inhibitor rolipram on cyclophosphamide-induced cystitis in rats.	2008 May 31	18358472
Prophylactic effect of irsogladine maleate against indomethacin-induced small intestinal lesions in rats.	2008 Oct	18306037
Phosphodiesterase isozymes involved in regulating acid secretion in the isolated mouse stomach.	2009 Dec	20388963
Rolipram, a specific type-4 phosphodiesterase inhibitor, inhibits cyclophosphamide-induced haemorrhagic cystitis in rats.	2009 Jan	18710439
Regulation of AMP-activated protein kinase by cAMP in adipocytes: roles for phosphodiesterases, protein kinase B, protein kinase A, Epac and lipolysis.	2009 May	19167487
Anti-inflammatory properties of Septilin in lipopolysaccharide activated monocytes and macrophage.	2011 Mar	20384571
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 Sep 1	23782265
Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network.	2014 Apr 25	24771768

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 `Fri Dec 15 15:32:19 GMT 2023` Edited by `admin` on `Fri Dec 15 15:32:19 GMT 2023`
Record UNII	K676NL63N7
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ROLIPRAM

Official Name

English

ROLIPRAM [MI]

Common Name

English

(±)-ROLIPRAM

Common Name

English

SB-95952

Code

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