(S)-(+)-Rolipram, known as (+)-Rolipram, is a selective inhibitor of cyclic AMP (cAMP)-specific phosphodiesterase 4 (PDE4) with an IC50 of 1100 nM. It is effective in suppressing tumor necrosis factor-alpha (TNFα) production in human mononuclear cells[1].[2].[3].
体内研究
Moreover, (+)-Rolipram (0.025-6.25 mg/kg; a single i.p. injection) reduces locomotor activity and induces head twitches in rats in a dose-dependent manner[2].
In further studies, (+)-Rolipram (0.06-25 mg/kg; a single i.p. injection) leads to a dose-related decrease in the rectal temperature of rats[2].
体外研究
In laboratory settings, (+)-Rolipram (0.015-1000 μM; 20 h) has shown a dose-dependent ability to inhibit LPS-induced TNF production in human mononuclear cells, with an IC50 value of 550 nM[1].
(S)-(+)-Rolipram/(S)-(+)-咯利普兰 细胞实验
Cell Line
Concentration
Treated Time
Description
References
mouse primordial germ cell-like cells (PGCLCs)
10 μM
7 days
Screening for chemicals that promote PGCLC proliferation, (S)-(+)-Rolipram was found to significantly promote PGCLC proliferation
EMBO J. 2017 Jul 3;36(13):1888-1907
hippocampal slices
0.1µM
60 min
To investigate the rescuing effect of rolipram on LTP deficits caused by sleep deprivation, results showed that rolipram rescued the LTP deficits caused by sleep deprivation
Nature. 2009 Oct 22;461(7267):1122-5
Adult feline left ventricular myocytes
1 μM
To evaluate the effect of rolipram on ISO-mediated cAMP generation, results showed that rolipram significantly enhanced ISO-induced cAMP generation.
Circulation. 2014 Nov 11;130(20):1800-11
hippocampal slices
1 μM
20 min
To test the effect of rolipram on LTP deficits in hippocampal slices from APP/PS1 mice. Results showed that rolipram significantly ameliorated LTP deficits in APP/PS1 hippocampal slices, bringing LTP levels close to those of wild-type mice.
J Clin Invest. 2004 Dec;114(11):1624-34
CHO cells
0.1, 0.25, 0.5, 1.0, and 2.0 μM
18 h
Rolipram overcame inhibition by 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.
hippocampal slices
0.03 μM, 0.3 μM, 3.0 μM
45 min
Low concentrations of rolipram had no significant effect on basal cAMP levels, but significantly amplified the cAMP response to forskolin stimulation.
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15020-5
(S)-(+)-Rolipram/(S)-(+)-咯利普兰 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Sleep deprivation model
Intraperitoneal injection
1 mg/kg
Injected immediately and 2.5 hours after training
To investigate the rescuing effect of rolipram on memory deficits caused by sleep deprivation, results showed that rolipram rescued the memory deficits caused by sleep deprivation
Nature. 2009 Oct 22;461(7267):1122-5
Mice
APP/PS1 double-transgenic mice
Subcutaneous injection
0.03 mg/kg
Acute administration: single dose 30 minutes before testing; Long-term administration: daily dose of 0.03 mg/kg for 3 weeks, followed by 6-8 weeks of withdrawal before testing.
To test the acute and long-term effects of rolipram on cognitive and synaptic functions in APP/PS1 mice. Acute administration significantly improved contextual fear conditioning deficits in APP/PS1 mice but had no significant effect on spatial working memory. Long-term administration significantly improved synaptic function (BST and LTP) and multiple cognitive functions (including associative learning, working memory, and reference memory) in APP/PS1 mice, with effects lasting at least 2 months after treatment cessation.
J Clin Invest. 2004 Dec;114(11):1624-34
Mice
C57/Bl6 mice
Subcutaneous injection
0.1 μmol/kg, 3.0 μmol/kg
30 min before training
Low-dose rolipram significantly enhanced long-term memory (24-hr freezing), while high doses caused behavioral toxicity.
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15020-5
Sprague-Dawley rats
Acute and subacute inflammation models
Intraperitoneal injection
8 mg/kg
Single dose, observed for 60 min or 4 h
Rolipram significantly inhibited PAF or LPS-induced leukocyte rolling, adhesion, and emigration, and downregulated P- and E-selectin expression, but had no effect on ICAM-1 and VCAM-1 expression.
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