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Chemical Structure| 61413-54-5 Chemical Structure| 61413-54-5

Structure of Rolipram
CAS No.: 61413-54-5

Chemical Structure| 61413-54-5

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Rolipram is a selective inhibitor of phosphodiesterases PDE 4, especially the PDE 4B with IC50 of 130 nM while IC50 for PDE4D is 240 nM, it's an anti-inflammatory agent.

Synonyms: (R,S)-Rolipram; ZK 62711; ME-3167

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Product Details of Rolipram

CAS No. :61413-54-5
Formula : C16H21NO3
M.W : 275.34
SMILES Code : O=C1NCC(C2=CC=C(OC)C(OC3CCCC3)=C2)C1
Synonyms :
(R,S)-Rolipram; ZK 62711; ME-3167
MDL No. :MFCD00270906
InChI Key :HJORMJIFDVBMOB-UHFFFAOYSA-N
Pubchem ID :5092

Safety of Rolipram

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • PDE4

    PDE4B, IC50:130 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
J774 mouse macrophage cell line 2 µM 1 hour Rolipram enhanced LPS-induced MKP-1 mRNA and protein expression and inhibited p38 MAPK phosphorylation. Br J Pharmacol. 2013 Aug;169(7):1525-36.
Primary mouse peritoneal macrophages 2 µM 1 hour Rolipram enhanced LPS-induced MKP-1 mRNA expression. Br J Pharmacol. 2013 Aug;169(7):1525-36.
Human eosinophils 0.03-0.2 µM 15 minutes To investigate the effect of Rolipram on PAF- and C5a-stimulated LTC4 synthesis in human eosinophils, results showed that Rolipram significantly inhibited LTC4 synthesis. Br J Pharmacol. 1996 Aug;118(7):1727-35.
DRG neurons 0.1, 0.25, 0.5, 1.0, and 2.0 µM 18 hours Rolipram overcame inhibition by both MAG and myelin in a dose-dependent manner, completely blocking inhibition by MAG at 0.5 µM. Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8786-90.
CHO cells 0.1, 0.25, 0.5, 1.0, and 2.0 µM 18 hours Rolipram overcame inhibition by both MAG and myelin in a dose-dependent manner, completely blocking inhibition by MAG at 0.5 µM. Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8786-90.
LX2 human hepatic stellate cells 10 µM 24 hours Rolipram significantly attenuated TGF β1-mediated cell migration/wound closure J Pathol. 2023 Nov;261(3):361-371.
U251 cells 100 µM 48 hours To evaluate the cytotoxic effect of NEO214 on U251 cells, results showed that NEO214 was cytotoxic to both TMZ-sensitive and TMZ-resistant glioma cells. Autophagy. 2023 Dec;19(12):3169-3188.
U251TR cells 100 µM 48 hours To evaluate the cytotoxic effect of NEO214 on U251TR cells, results showed that NEO214 was cytotoxic to both TMZ-sensitive and TMZ-resistant glioma cells. Autophagy. 2023 Dec;19(12):3169-3188.
T98G cells 100 µM 48 hours To evaluate the cytotoxic effect of NEO214 on T98G cells, results showed that NEO214 was cytotoxic to both TMZ-sensitive and TMZ-resistant glioma cells. Autophagy. 2023 Dec;19(12):3169-3188.
Rat mixed neural cell myelinating cultures 10 nM–10 µM 7 days Rolipram enhanced neurite density in areas closely surrounding the lesion and induced significant neurite outgrowth across the lesion over a broad concentration range of 10 nM–10 μM. Rolipram enhanced myelination surrounding the lesion at a concentration range of 10–50 nM, but inhibited myelination at higher concentrations. Br J Pharmacol. 2014 May;171(9):2385-98.
oligodendrocyte progenitor cells (OPCs) 0.5 µM 48 h rolipram promotes OPC differentiation in the presence of myelin-associated inhibitors, increasing O4 and Mbp expression EMBO Mol Med. 2013 Dec;5(12):1918-34

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
ICR mice Antidepressant- and anxiolytic-like behavior model Intraperitoneal injection 0.31, 0.62, 1.25 mg/kg Once daily for 17-23 days Rolipram produced antidepressant- and anxiolytic-like effects on behavior by increasing cAMP and pCREB levels in the hippocampus and prefrontal cortex, and increasing Sox2 expression in the hippocampus. Neuropsychopharmacology. 2009 Oct;34(11):2404-19
Long Evan Hooded rats Spinal cord hemisection model Subcutaneous injection 0.4 or 0.8 µmol/kg per hour Continuous for 10 days Rolipram significantly promoted axon regeneration, attenuated the formation of the glial scar, and significantly enhanced functional recovery. Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8786-90.
Sprague- Dawley rats Conscious and anesthetized rats Intravenous infusion 0–1 mg/kg 60 minutes To measure the binding site density (B max) and radioligand affinity (1/K D) of 11C-(R)-rolipram in the rat brain, and to study the differences in binding between conscious and anesthetized states. Results showed that B max and K D were significantly higher in conscious rats compared to anesthetized rats, and the in vitro K D was 3–7 times greater than the in vivo K D. J Nucl Med. 2009 May;50(5):749-56
C57BL/6 mice Carrageenan-induced paw inflammation model Intraperitoneal injection 100 mg/kg Single dose, 3 hours duration Rolipram significantly attenuated carrageenan-induced paw inflammation in WT mice but had no significant effect in MKP-1(–/–) mice. Br J Pharmacol. 2013 Aug;169(7):1525-36.
Sprague- Dawley rats Bone cancer pain model Intrathecal injection 12.5, 25, 50, 100 µg/kg Daily injection for 7 days Rolipram significantly alleviated mechanical allodynia and thermal hyperalgesia in rats with bone cancer pain by inhibiting the spinal JNK/CCL2 signaling pathway and astrocytic activation Int J Mol Med. 2016 Nov;38(5):1433-1442
BALB/c mice LPS-induced lung inflammation model Intraperitoneal injection 20 mg/kg Single injection, lasting 45 minutes To investigate the effect of Rolipram on LPS-induced lung inflammation, the results showed that Rolipram significantly reduced TNF-α levels in the BALF and almost completely inhibited LPS-induced neutrophil infiltration. Br J Pharmacol. 1998 Feb;123(4):631-6
Athymic rats C5 hemisection model Local delivery 25 µg/ml, 500 µg/ml Single administration, lasted for 8 weeks To evaluate the functional and anatomical recovery effects of Rolipram on spinal cord injury repair. Low-dose Rolipram significantly improved functional and anatomical recovery, while high-dose Rolipram was similar to the untreated group and resulted in reduced animal survival rates. J Control Release. 2012 Aug 10;161(3):910-7
C57BL/6J mice CCl4-induced liver fibrosis model Targeted hepatic delivery 3.3 mg/kg 24 hours after each CCl4 administration, for 4 weeks Rolipram attenuated SMAD3 signaling and stellate cell activation marker αSMA, reduced collagen deposition J Pathol. 2023 Nov;261(3):361-371.
Balb/C mice Klebsiella pneumoniae infection model Oral 3–30 mg/kg Administered 24 and 2 hours prior to infection and daily thereafter To assess the effects of rolipram on the antibacterial host response in mice infected with Klebsiella pneumoniae. Results showed that rolipram treatment was associated with earlier lethality and significant inhibition of TNF-α production, along with enhanced IL-10 production in lung tissue. Rolipram treatment did not affect KC expression and neutrophil recruitment in lung tissue but inhibited neutrophil phagocytosis of K. pneumoniae. Br J Pharmacol. 2003 Nov;140(5):855-62
Nude mice Intracranial glioma model Subcutaneous injection 50 mg/kg 30 days, 5 days on, 2 days off To evaluate the anti-tumor effect of NEO214 in an intracranial glioma model, results showed that NEO214 significantly delayed tumor growth and prolonged the survival of mice. Autophagy. 2023 Dec;19(12):3169-3188.
Sprague- Dawley rats Acute inflammation model Intraperitoneal injection 8 mg/kg Single dose, 30 minutes before the experiment Rolipram significantly inhibited PAF and LPS-induced leukocyte rolling, adhesion, and emigration by 100%, 95%, and 95%, respectively. Additionally, Rolipram reversed the decrease in leukocyte rolling velocity induced by PAF. Br J Pharmacol. 2002 Apr;135(8):1872-81

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01805518 Adverse Mental/Physical Effect... More >>s of Low Dose S. Tortuosum. Less << Phase 1 Completed - Puerto Rico ... More >> Michel A. Woodbury, MD San Juan, Puerto Rico, 00918 Less <<
NCT02743377 Nervous System Disease Phase 1 Phase 2 Recruiting March 25, 2020 United States, Maryland ... More >> National Institutes of Health Clinical Center Recruiting Bethesda, Maryland, United States, 20892 Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov Less <<
NCT01602900 Huntington Disease Phase 1 Completed - United Kingdom ... More >> GSK Investigational Site London, United Kingdom, NW10 7EW GSK Investigational Site London, United Kingdom, W12 ONN Less <<
NCT00250172 Dosimetry Hea... More >>lthy Less << Phase 1 Completed - United States, Maryland ... More >> National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland, United States, 20892 Less <<
NCT01215552 Healthy Elderly Volunteers Phase 1 Terminated(The experimental de... More >>sign was not sufficient to answer the proposed questions. A new study design is now being considered.) Less << - United States, New York ... More >> Brookhaven National Laboratory Upton, New York, United States, 11973 Less <<
NCT00011375 Multiple Sclerosis PHASE2 COMPLETED 2025-04-04 National Institute of Neurolog... More >>ical Disorders and Stroke (NINDS), Bethesda, Maryland, 20892, United States Less <<
NCT00369798 Major Depressive Disorder ... More >> Healthy Less << Phase 1 Completed - United States, Maryland ... More >> National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland, United States, 20892 Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.63mL

0.73mL

0.36mL

18.16mL

3.63mL

1.82mL

36.32mL

7.26mL

3.63mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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