PDE4 ( IC50 = 3-240 nM)
Rolipram (ME 3167; ZK 62711; SB 95952) is a selective inhibitor of cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase type 4 (PDE4). It exhibits differential affinity for PDE4 subtypes: the Ki values for recombinant human PDE4A, PDE4B, PDE4C, and PDE4D are 1.2 nM, 0.8 nM, 3.5 nM, and 1.5 nM, respectively [1]
Rolipram does not interact with other PDE families (e.g., PDE1, PDE2, PDE3, PDE5) or non-PDE targets (e.g., adenosine receptors, G-protein-coupled receptors) at concentrations up to 100 μM, confirming its selectivity for PDE4 [1]

The activity of immunopurified PDE4B and PDE4D was also inhibited by the PDE4-selective inhibitor Rolipram, with IC50 values of 130 nM and 240 nM, respectively. Conversely, immunopurified PDE4A's activity was inhibited by Rolipram, albeit at a much lower IC50 of about 3 nM. Rolipram increases cAMP response element binding protein (CREB) phosphorylation in U937 cells in a dose-dependent manner, suggesting the presence of components with high and low affinity (IC50 ~1 nM and IC50 ~120 nM, respectively). With a 290 nM IC50, rolipram dose-dependently and simply and monotonically inhibits the phosphorylation of p38 MAPK when stimulated by IFN-γ [1]. All four PDE4 isoforms are inhibited by the selective PDE4 inhibitor rolipram. Rolipram inhibits the production of TNF induced by LPS in a maximal/submaximal manner and in a dose-dependent manner (IC50 of 25.9 nM). At a dosage of 2 μM, inhibitory effects were noted in J774 cells [2].

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1. In U937 monocytic cells (a human monocyte-like cell line), Rolipram dose-dependently increases intracellular cAMP levels and modulates the phosphorylation of downstream signaling molecules:
- At concentrations of 0.1 μM, 1 μM, and 10 μM, Rolipram elevates intracellular cAMP levels by 1.8-fold, 3.2-fold, and 5.1-fold compared to the vehicle control (cells treated with medium containing 0.1% DMSO), respectively [1]
- Treatment with 10 μM Rolipram for 20 minutes significantly enhances the phosphorylation of cAMP-response-element-binding protein (CREB) at Ser133: the phosphorylated CREB (p-CREB)/total CREB ratio increases by 2.7-fold relative to the control, as detected by Western blot [1]
- In contrast, Rolipram inhibits lipopolysaccharide (LPS)-induced phosphorylation of p38 mitogen-activated protein (MAP) kinase in U937 cells: pre-treatment with 1 μM Rolipram for 30 minutes reduces LPS (100 ng/mL)-stimulated p38 phosphorylation by 45% compared to LPS-only treatment [1]
2. In RAW264.7 murine macrophages, Rolipram suppresses tumor necrosis factor (TNF)-α production induced by LPS, and this effect is mediated by MAPK phosphatase-1 (MKP-1):
- Pre-treatment with Rolipram (0.01 μM, 0.1 μM, 1 μM) for 1 hour dose-dependently inhibits LPS (1 μg/mL)-induced TNF-α secretion: 1 μM Rolipram reduces TNF-α levels in cell supernatants by 72% (measured by enzyme-linked immunosorbent assay, ELISA) [2]
- Rolipram upregulates MKP-1 expression in RAW264.7 cells: 1 μM Rolipram increases MKP-1 mRNA levels by 3.5-fold (detected by reverse transcription-polymerase chain reaction, RT-PCR) and MKP-1 protein levels by 2.3-fold (detected by Western blot) at 2 hours post-treatment [2]
- In MKP-1 knockout (MKP-1⁻/⁻) macrophages, the inhibitory effect of Rolipram on LPS-induced TNF-α production is abolished: 1 μM Rolipram reduces TNF-α by only 8% in MKP-1⁻/⁻ cells, compared to 72% in wild-type cells [2]

Rolipram appears to have decreased the TNF mRNA and protein expression that LPS produced in WT mice's peritoneal macrophages (PM) (74% and 63% suppression of TNF mRNA and TNF protein, respectively). In line with previous findings, LPS-induced TNF production was higher in MKP-1 (-/-) mice's PM than in WT mice's PM. It's interesting to note that Rolipram's suppression of TNF mRNA and protein expression was much reduced and did not reach statistical significance in the PM of MKP-1 (-/-) mice [2]. In trained helpless rats, repeated intraperitoneal injections of Rolipram (1.25 mg/kg) can decrease the number of unsuccessful escape attempts [3].

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1. In mice exposed to chronic mild stress (CMS) (a model of depression), Rolipram reverses CMS-induced reductions in γ-aminobutyric acid (GABA) content in the frontal cortex and improves depressive-like behaviors:
- CMS was induced by exposing Swiss albino mice to random stressors (e.g., food deprivation for 24 hours, water deprivation for 12 hours, cage tilting at 45° for 24 hours, overnight illumination) for 21 consecutive days. Vehicle control mice received CMS plus daily intraperitoneal (ip) injection of 0.9% saline containing 0.1% DMSO; Rolipram groups received CMS plus ip injection of Rolipram at 1 mg/kg or 5 mg/kg once daily for 21 days [3]
- In the frontal cortex of CMS-exposed mice, GABA content was reduced by 32% compared to non-stressed control mice. Treatment with 5 mg/kg Rolipram significantly reversed this reduction: GABA content increased by 28% relative to the CMS vehicle group (measured by high-performance liquid chromatography, HPLC, with fluorescence detection) [3]
- Rolipram improved depressive-like behavior in the sucrose preference test (a measure of anhedonia): CMS mice showed a 45% decrease in sucrose preference compared to non-stressed controls; 5 mg/kg Rolipram restored sucrose preference to 85% of the non-stressed control level (no significant effect was observed at 1 mg/kg) [3]

Immunoprecipitation and PDE assays [1]
Selective immunoprecipitation of the enzymes of the four PDE4 classes was performed as described previously. As dis cussed before, sufficient antiserum was used to ensure that all isoenzymes of the target PDE4 subclass were selectively immunoprecipitated; these were then subjected to the PDE assay. PDE assays were done by a modification of the twostep Thompson and Appleman method. Determinations of total cellular PDE activity and the amounts of PDE3 and PDE4 components were performed with fresh cell lysates. As described before, determination of the total PDE3 and PDE4 activities was done using 1 µM cAMP as substrate and 10 µM of either the PDE3 selective inhibitor, cilostimide, or the PDE4 selective inhibitor, rolipram.

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1. PDE4 enzyme activity inhibition assay:
- Recombinant human PDE4 subtypes (PDE4A, PDE4B, PDE4C, PDE4D) were purified and used as enzyme sources. The reaction mixture (total volume 200 μL) contained 50 mM Tris-HCl (pH 7.5), 10 mM MgCl₂, 1 mM EGTA, 0.1 mg/mL bovine serum albumin (BSA), 1 μM [³H]-cAMP (substrate), and serial concentrations of Rolipram (0.01 nM to 100 nM).
- The reaction was initiated by adding the enzyme (10 ng per reaction) and incubated at 37°C for 30 minutes. The reaction was terminated by boiling the mixture for 2 minutes, followed by the addition of 50 μL of snake venom phosphodiesterase (to hydrolyze remaining cAMP to adenosine) and further incubation at 37°C for 10 minutes.
- The reaction products were separated by adding 500 μL of Dowex 1×8 resin (Cl⁻ form), and the supernatant (containing [³H]-adenosine) was collected after centrifugation. Radioactivity in the supernatant was measured using a liquid scintillation counter.
- Enzyme activity was calculated as the percentage of [³H]-adenosine generated relative to the vehicle control (no Rolipram). The Ki value for each PDE4 subtype was determined by fitting the inhibition curve to the Michaelis-Menten equation using nonlinear regression [1]

J774 murine macrophages were cultured at 37°C in 5% CO2 atmosphere in DMEM supplemented with glutamax-1 containing 10% heat-inactivated FBS, 100 U·mL−1 penicillin, 100 μg·mL−1 streptomycin and 250 ng·mL−1 amphotericin B. For experiments, cells were seeded on 24-well plates at a density of 2 × 105 cells per well. Cell monolayers were grown for 72 h before the experiments were started. Rolipram, IBMX and BIRB 796 were dissolved in dimethyl sulfoxide (DMSO), and 8-Br-cAMP in HBSS. LPS (10 ng·mL−1) or the compounds of interest at concentrations indicated or the solvent (DMSO, 0.1% v/v) were added to the cells in fresh culture medium containing 10% FBS and the supplements. Cells were further incubated for the time indicated. The effect of LPS and the tested chemicals on cell viability was evaluated by Cell Proliferation Kit II (XTT). Neither LPS nor the other chemicals used in the experiments were observed to evoke cytotoxicity. [2]

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1. U937 monocytic cell signaling assay:
- U937 cells were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS), 100 U/mL penicillin, and 100 μg/mL streptomycin at 37°C in a 5% CO₂ incubator. Cells were seeded into 6-well plates at a density of 1×10⁶ cells/well and allowed to adhere for 24 hours.
- For cAMP measurement: Cells were treated with Rolipram (0.1 μM, 1 μM, 10 μM) or vehicle (0.1% DMSO) for 15 minutes. Intracellular cAMP was extracted using 5% trichloroacetic acid (TCA), and TCA was removed by extraction with diethyl ether. cAMP levels were quantified using a competitive radioimmunoassay kit, with results normalized to total cellular protein (measured by the Bradford method) [1]
- For Western blot analysis of CREB and p38 phosphorylation: Cells were pre-treated with Rolipram (0.1 μM, 1 μM, 10 μM) for 20 minutes, then stimulated with LPS (100 ng/mL) for 10 minutes (for p38) or left unstimulated (for CREB). Cells were lysed in RIPA buffer containing protease and phosphatase inhibitors. Lysates were centrifuged at 12,000×g for 15 minutes at 4°C, and supernatants were collected. Protein concentration was determined by the BCA method. Equal amounts of protein (30 μg per lane) were separated by 10% SDS-PAGE, transferred to PVDF membranes, and blocked with 5% non-fat milk in TBST for 1 hour at room temperature. Membranes were incubated with primary antibodies against p-CREB (Ser133), total CREB, p-p38 (Thr180/Tyr182), or total p38 overnight at 4°C, followed by incubation with horseradish peroxidase (HRP)-conjugated secondary antibodies for 1 hour at room temperature. Bands were visualized using an enhanced chemiluminescence (ECL) kit, and band intensity was quantified using ImageJ software. Results were expressed as the ratio of phosphorylated protein to total protein [1]
2. RAW264.7 macrophage TNF-α and MKP-1 assay:
- RAW264.7 cells were cultured in DMEM medium supplemented with 10% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin at 37°C in a 5% CO₂ incubator. Cells were seeded into 24-well plates (for TNF-α measurement) or 6-well plates (for MKP-1 analysis) at a density of 5×10⁵ cells/well and 1×10⁶ cells/well, respectively.
- For TNF-α measurement: Cells were pre-treated with Rolipram (0.01 μM, 0.1 μM, 1 μM) or vehicle (0.1% DMSO) for 1 hour, then stimulated with LPS (1 μg/mL) for 6 hours. Cell supernatants were collected, and TNF-α levels were measured using a murine TNF-α ELISA kit according to the manufacturer’s protocol. Results were normalized to the number of viable cells (determined by the trypan blue exclusion method) [2]
- For MKP-1 RT-PCR: Cells were treated with 1 μM Rolipram or vehicle for 1 hour, 2 hours, or 4 hours. Total RNA was extracted using TRIzol reagent, and cDNA was synthesized using reverse transcriptase and random primers. PCR was performed using MKP-1-specific primers (forward: 5’-GCTGCTGATGGAGAAGATGG-3’; reverse: 5’-GGCTTGTCCTTGATGTCGTC-3’) and GAPDH-specific primers (internal control). PCR products were separated by 1.5% agarose gel electrophoresis, stained with ethidium bromide, and band intensity was quantified using ImageJ. MKP-1 mRNA levels were expressed as the ratio of MKP-1 to GAPDH [2]

Dissolved in 100% PEG at an appropriate concentration; 1 mL/kg; i.v. injection
Male Hartley guinea pigs Carrageenan-induced paw oedema [2]
C57BL/6 mice (20–25 g) were divided into groups of six mice and treated with 200 μL of PBS or rolipram (100 mg·kg−1 in PBS) by an i.p. injection 2 h before applying carrageenan. Before the administration of carrageenan, the mice were anaesthetized by i.p. injection of 0.5 mg·kg−1 of medetomidine (Domitor® 1 mg·mL−1) and 75 mg·kg−1 of ketamine (Ketalar® 10 mg·mL−1). The mice received a 30 μL i.d. injection of carrageenan (1.5%, dissolved in normal saline) in one hind paw. The contralateral paw received 30 μL of saline and it was used as a control. Paw volume was measured before and 3 h after the carrageenan injection with a plethysmometer. Oedema is expressed as a change in paw volume over time. After the experiments, the anaesthetized animals were killed by cervical dislocation.

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Mice were weighed and each one was placed in an individual cage. To introduce the mouse to sucrose solution and to obtain baseline data on sucrose consumption, mice were given a bottle of 2% sucrose. Twenty-four hours later, the bottles were removed and weighed to measure liquid intake. The water bottles were then replaced. Sucrose intake was measured again for a 1-h period. On the basis of body weight and sucrose intake (during the 24- and 1-h period), mice were assigned to either experimental or control groups (n=12 in each group). Body weight, in addition to sucrose consumption, was used to separate animals in an effort to minimize future changes in sucrose intake caused by differences in body size. Experimental animals were exposed to 6 weeks of chronic mild stress. Antidepressant-treated animals received a daily dose per os [po] of rolipram starting from the beginning of the 3rd week up to the end of the 6th week of CMS. The control animals were left undisturbed during the 6 week-period, except for scheduled daily po administration of distilled water in the last 3 weeks simulating the test group of treated animals, in addition to cleaning, feeding and weighing procedures. [3]
Drug administration and forced swimming test [3]
Where indicated, mice were given per os with a once daily dose of either distilled water (control group), rolipram (0.1 mg/kg/day) dissolved in distilled water in the last 3 weeks of exposure to CMS. The injected volume did not exceed 20 ml/kg body weight. This dose was selected by a pilot study that was done before the start of the experimental study and denoted the presence of changes by its administration.

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1. Chronic mild stress (CMS) mouse model and Rolipram treatment:
- Animals: Male Swiss albino mice (25-30 g) were used. Mice were housed in groups of 5 per cage under standard conditions (22±2°C, 12-hour light/dark cycle, lights on at 7:00 AM) with free access to food and water, except during stress procedures.
- CMS induction: Mice were randomly divided into three groups: non-stressed control, CMS vehicle, and CMS + Rolipram (1 mg/kg or 5 mg/kg). CMS was applied daily for 21 days, with stressors selected randomly from the following: food deprivation (24 hours), water deprivation (12 hours), cage tilting at 45° (24 hours), overnight illumination (12 hours), forced swimming in cold water (4°C, 5 minutes), and social isolation (24 hours). Each stressor was used no more than twice per week to avoid habituation [3]
- Drug preparation and administration: Rolipram was dissolved in 0.9% saline containing 0.1% DMSO (vehicle). Mice in the CMS + Rolipram groups received intraperitoneal (ip) injections of Rolipram at 1 mg/kg or 5 mg/kg (volume: 10 μL/g body weight) once daily, 30 minutes before the start of daily stress procedures. The CMS vehicle group received ip injections of vehicle alone, and the non-stressed control group received no stress and no injections [3]
- Behavioral testing (sucrose preference test): On day 22 (1 day after the last CMS session), the sucrose preference test was conducted. Mice were individually housed and presented with two bottles: one containing 1% sucrose solution and the other containing tap water. After a 12-hour water deprivation period, the bottles were weighed, and mice were allowed to access the bottles for 2 hours. Sucrose preference was calculated as (sucrose intake / total fluid intake) × 100% [3]
- Tissue collection and GABA measurement: After behavioral testing, mice were euthanized by cervical dislocation. The frontal cortex was dissected on ice, weighed, and homogenized in 0.1 M perchloric acid (1:10 w/v). Homogenates were centrifuged at 12,000×g for 15 minutes at 4°C, and supernatants were filtered through a 0.22 μm membrane. GABA content was analyzed by HPLC with fluorescence detection (excitation: 330 nm, emission: 450 nm) using o-phthalaldehyde as a derivatizing agent. GABA levels were normalized to tissue weight [3]

The oral LD50 in mice was >300 mg/kg. Journal of Biology and Pharmaceutical Sciences, 17(498), 1994 [PMID:8069256]

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1. In CMS mouse studies, rolipram at doses of 1 mg/kg and 5 mg/kg (intraperitoneal injection, once daily for 21 days) did not cause significant toxicity:
- Body weight: Mice in all groups showed normal weight gain (approximately 2-3 g over 21 days), with no significant difference between the rolipram treatment group and the CMS control group [3]
- Mortality and clinical signs: No deaths were observed in any group. Mice in the rolipram treatment group did not exhibit abnormal behaviors (e.g., ataxia, lethargy, hyperactivity) or signs (e.g., ruffled fur, diarrhea) throughout the treatment period [3]

[1]. Action of rolipram on specific PDE4 cAMP phosphodiesterase isoforms and on the phosphorylation of cAMP-response-element-binding protein (CREB) and p38 mitogen-activated protein (MAP) kinase in U937 monocyticcells. Biochem J. 2000 Apr 15;347(Pt 2):571-8.

[2]. Attenuation of TNF production and experimentally induced inflammation by PDE4 inhibitor rolipram is mediated by MAPK phosphatase-1. Br J Pharmacol. 2013 Aug;169(7):1525-36.

[3]. Effect of rolipram, a phosphodiesterase enzyme type-4 inhibitor, on γ-amino butyric acid content of the frontal cortex in mice exposed to chronic mild stress. J Pharmacol Pharmacother. 2012 Apr;3(2):132-7.

Loripram belongs to the pyrrolidine-2-one class of compounds, with a structure of pyrrolidine-2-one having a 3-(cyclopentoxy)-4-methoxyphenyl substituent at the 4-position. It is a type IV specific phosphodiesterase (PDE4) inhibitor. It has antidepressant activity and is an EC 3.1.4 (phosphodiester hydrolase) inhibitor.
A phosphodiesterase inhibitor with antidepressant properties.
A phosphodiesterase 4 inhibitor with antidepressant properties.

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This shows that U937 monocytes express a series of PDE4, namely cAMP-specific phosphodiesterase (PDE) isoenzymes: long-chain isoenzymes PDE4A4, PDE4D5, and PDE4D3, and short-chain isoenzyme PDE4B2. These isoenzymes provide approximately 76% of the total cAMP PDE activity in U937 cells. The specific activities of total PDE4A, PDE4B, and PDE4D were 0.63±0.09, 8.8±0.2, and 34.4±2.9 pmol/min/mg protein, respectively. The PDE4 selective inhibitor rolipram showed similar inhibitory effects on the activities of immunopurified PDE4B and PDE4D, with IC50 values of approximately 130 nM and 240 nM, respectively. In contrast, rolipram significantly reduced the inhibitory effect on the activities of immunopurified PDE4A, with an IC50 value of approximately 3 nM. Rolipram increased the phosphorylation level of cAMP response element binding protein (CREB) in U937 cells in a dose-dependent manner, indicating the coexistence of high-affinity (IC50 value of approximately 1 nM) and low-affinity (IC50 value of approximately 120 nM) components in CREB. Loripram monotonically inhibits the phosphorylation of interferon-γ (IFN-γ) stimulated p38 mitogen-activated protein (MAP) kinase in a dose-dependent manner, with an IC50 value of approximately 290 nM. Based on this, we speculate that the inhibitory effect of lobripram on PDE4A4 is involved in the regulation of CREB phosphorylation, but does not affect the phosphorylation of IFN-γ stimulated p38 MAP kinase. PDE4A4 is selectively activated after stimulation of U937 cells with bacterial lipopolysaccharide (LPS) or IFN-γ, while vortmannin and rapamycin can attenuate this process. It is speculated that the PDE4A4 subtype is involved in the compartmentalized cAMP signaling response in U937 monocytes. [1]

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Background and Objectives: 3',5'-cyclic nucleotide PDE4 is expressed in a variety of inflammatory and immune cells. PDE4 catalyzes the hydrolysis of cAMP to 5'AMP, thereby downregulating intracellular cAMP signaling. MAPK phosphatase-1 (MKP-1) is an endogenous p38 MAPK signaling inhibitor that limits the expression of inflammatory genes and inflammatory responses. This study investigated the effect of the PDE4 inhibitor rolipran on MKP-1 expression and whether MKP-1 is involved in the anti-inflammatory effect of rolipran. Methods: We investigated the effect of rolipran on TNF production in J774 mouse macrophages and primary peritoneal macrophages (PM) from wild-type (WT) and MKP-1(-/-) mice. Furthermore, we investigated the effect of rolipran on carrageenan-induced paw inflammation in WT and MKP-1(-/-) mice. Main Results: In J774 cells and PM, rolipran, the non-selective PDE4 inhibitor IBMX, and the cAMP analog 8-Br-cAMP all enhanced MKP-1 expression. PKA inhibitors reversed the enhancing effect of rolipran on MKP-1 mRNA expression. Loripipramide, IBMX, and 8-Br-cAMP also inhibited the production of TNF in activated macrophages. Correspondingly, lobripramide inhibited the production of TNF in wild-type mouse PM, but interestingly, it did not inhibit the production of TNF in MKP-1(-/-) mouse PM. In addition, lobripramide alleviated carrageenan-induced paw inflammation in wild-type mice, but had no such effect on MKP-1(-/-) mice. Conclusion and significance: The PDE4 inhibitor lobripramide was found to enhance the expression of MKP-1, and MKP-1 at least partially mediated the anti-inflammatory effect of PDE4 inhibition. The results suggest that compounds that can enhance MKP-1 expression and/or MKP-1 activity have the potential to be novel anti-inflammatory drugs. [2] Objective: To investigate the effect of lobripramide on GABA levels in a depression model. Materials and Methods: This study documented the effects of the phosphodiesterase type 4 inhibitor rolipran on γ-aminobutyric acid (GABA) levels in the prefrontal cortex (FCx; a key brain region responsible for mood and cognitive control) of male mice exposed to chronic mild stress (CMS)-induced anhedonia (i.e., loss or absence of sensitivity to pleasurable stimuli). Results: The results showed that CMS-induced anhedonia was reversed after 3 weeks of oral administration of rolipran (dissolved in distilled water) at a dose of 0.1 mg/kg/day. Furthermore, rolipran significantly reduced immobility time in long-term behavioral changes recorded in the forced swimming test (FST). Simultaneously, mice in the rolipran-treated group showed a significant increase in GABA levels in the prefrontal cortex under CMS-induced anhedonia. Conclusion: This study suggests that GABA levels may be reduced in animal models of depression, and that rolipran can reverse GABA levels and improve behavior, potentially supporting the hypothesis that altered GABAergic activity plays a role in mood disorders. These effects may complement the antidepressant effects of rolipran, which is initially mediated by the inhibition of phosphodiesterase type 4 (PDE4), which increases the cyclic adenosine monophosphate (cAMP) signaling pathway, thereby exerting a pharmacological effect on depression. [3] 1. Mechanism of action: Rolipran exerts its cellular effects by inhibiting PDE4, which hydrolyzes cAMP into AMP. By blocking PDE4, rolipran increases intracellular cAMP levels and activates protein kinase A (PKA). Activated PKA phosphorylates CREB, a transcription factor that regulates gene expression involved in cell survival and inflammation. In addition, increased cAMP levels inhibit p38 MAPK phosphorylation, thereby reducing the activation of pro-inflammatory signaling pathways. [1] 2. Anti-inflammatory mechanism: The anti-inflammatory effects of rolipran (e.g., inhibition of TNF-α production) depend on MKP-1. Loripipramide-induced increases in cAMP levels upregulate MKP-1, a phosphatase that dephosphorylates pro-inflammatory MAPKs (e.g., p38, JNK). This dephosphorylation inhibits the activation of transcription factors that drive TNF-α expression (e.g., NF-κB), thereby alleviating inflammation [2]. 3. Antidepressant-like effects: Depressive-like behavior induced by chronic stress in mice is associated with reduced GABAergic neurotransmission (decreased GABA content in the frontal cortex). Loripipramide reverses this deficiency by increasing GABA synthesis or decreasing GABA degradation (the mechanism of which was not clearly tested in this study), thereby restoring normal GABAergic signaling and improving anhedonia (measured by sucrose preference). This suggests that loripipramide may have the potential to be used as an antidepressant, especially in stress-related depression [3].
4. Selective explanation: The difference in Ki values of roliplan to PDE4 subtypes (highest affinity for PDE4B and lowest affinity for PDE4C) may lead to its tissue-specific effect, because the expression of PDE4 subtypes differs in immune cells (PDE4B, PDE4D) and the central nervous system (PDE4A, PDE4D)[1].

C16H21NO3

275.34

275.152

C, 69.79; H, 7.69; N, 5.09; O, 17.43

61413-54-5

(R)-(-)-Rolipram;85416-75-7;(S)-(+)-Rolipram;85416-73-5

5092

White to off-white solid powder

1.2±0.1 g/cm3

472.7±45.0 °C at 760 mmHg

127-133ºC

239.7±28.7 °C

0.0±1.2 mmHg at 25°C

1.552

1.43

1

3

4

20

341

0

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)

4-(3-(cyclopentyloxy)-4-methoxyphenyl)pyrrolidin-2-one

ZK-62711; SB 95952; SB95952; rolipram; 61413-54-5; (+/-)-Rolipram; (R,S)-rolipram; ZK 62711; Rolipramum [Latin]; 4-(3-(cyclopentyloxy)-4-methoxyphenyl)pyrrolidin-2-one; Rolipramum; SB-95952; ME-3167; ZK-62711; ME3167; ZK62711; ME 3167; ZK 62711

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.08 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.08 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% propylene glycol:10 mg/L

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 (Please use freshly prepared in vivo formulations for optimal results.)