(S)-(+)-Rolipram ((+)-Rolipram) is a cyclic AMP(cAMP)-specific phosphodiesterase 4 (PDE4) inhibitor, with an IC50 of 1100 nM. (S)-(+)-Rolipram can suppresse tumor necrosis factor-alpha (TNFα) production by human mononuclear cells[1][2][3].
IC50 & Target[1]
PDE4
1100 nM (IC50)
体外研究 (In Vitro)
(+)-Rolipram (0.015-1000 μM; 20 h) dose-dependently suppress LPS-induced TNF production of human mononuclear cells (MNC), with an IC50 of 550 nM[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
(+)-Rolipram (0.025-6.25 mg/kg; a single i.p.) dose-dependently inhibits locomotor activity and induces head twitches in rats[2]. (+)-Rolipram (0.06-25 mg/kg; a single i.p.) causes a dose-related fall in rectal temperature of rats[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
275.34
Formula
C16H21NO3
CAS 号
85416-73-5
中文名称
(S)-(+)-咯利普兰;(+)-咯利普兰
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Semmler J, et, al. The specific type IV phosphodiesterase inhibitor rolipram suppresses tumor necrosis factor-alpha production by human mononuclear cells. Int J Immunopharmacol. 1993 Apr;15(3):409-13.
[2]. Wachtel H. Neurotropic effects of the optical isomers of the selective adenosine cyclic 3′,5′-monophosphate phosphodiesterase inhibitor rolipram in rats in-vivo. J Pharm Pharmacol. 1983 Jul;35(7):440-4.
[3]. Ortmann R, et, al. Rolipram forms a potent discriminative stimulus in drug discrimination experiments in rats. Psychopharmacology (Berl). 1986;89(3):273-7.
The PDE4 selective inhibitor, Rolipram, inhibits immunopurified PDE4B and PDE4D activities similarly, with IC50s of approx. 130 nM and 240 nM respectively. In contrast, Rolipram inhibits immunopurified PDE4A activity with a dramatically lower IC50 of around 3 nM. Rolipram increases phosphorylation of cAMP-response-element-binding protein (CREB) in U937 cells in a dose-dependent fashion, which implies the presence of both high affinity (IC50 approx. 1 nM) and low affinity (IC50 approx. 120 nM) components. Rolipram dose-dependently inhibits the IFN-gamma-stimulated phosphorylation of p38 MAPK in a simple monotonic fashion with an IC50 of approx. 290 nM[1]. Rolipram is a selective PDE4 inhibitor that inhibits all PDE4 isoforms A, B, C and D. Rolipram inhibits LPS-induced TNF production in a dose-dependent manner (IC50 25.9 nM), and maximal/submaximal inhibition is observed with 2 μM drug concentration in J774 cells[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
TNF mRNA and protein expression is induced by LPS in peritoneal macrophages (PM) from WT mice, and that is clearly (by 74 and 63% for TNF mRNA and TNF protein, respectively) inhibited by Rolipram. LPS-induced TNF production is enhanced in PM from MKP-1(-/-) mice as compared to that in PM from WT mice, which is in line with the published results. Interestingly, the inhibition of TNF mRNA and protein expression by Rolipram is markedly attenuated in PM from MKP-1(-/-) mice and does not reach statistical significance[2]. Repeated administration of Rolipram (1.25 mg/kg, i.p.) reduces the number of escape failures in learned helplessness rats[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
275.34
Formula
C16H21NO3
CAS 号
61413-54-5
中文名称
咯利普兰
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : ≥ 41 mg/mL (148.91 mM)
H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)
[1]. MacKenzie SJ, et al. 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
[2]. Korhonen R, et al. 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]. Shalaby AM, et al. 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.
Cell Assay [2]
J774 murine macrophages (ATCC) are cultured at 37°C in 5% CO2 atmosphere in DMEM supplemented with glutamax-1 containing 10% heat-inactivated FBS. For experiments, cells are seeded on 24-well plates at a density of 2×105 cells per well. Cell monolayers are grown for 72 h before the experiments are started. Rolipram, IBMX and BIRB 796 are dissolved in DMSO, and 8-Br-cAMP in HBSS. LPS (10 ng/mL) or the compounds of interest at concentrations indicated or the solvent (DMSO, 0.1% v/v) are added to the cells in fresh culture medium containing 10% FBS and the supplements. Cells are further incubated for the time indicated. The effect of LPS and the tested chemicals on cell viability is evaluated by Cell Proliferation Kit II (XTT)[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [2]
Mice[2] Inbred C57BL/6 MKP-1(-/-) mice are used. C57BL/6 mice (20-25 g) are divided into groups of six mice and treated with 200 μL of PBS or Rolipram (100 mg/kg in PBS) by an i.p. injection 2 h before applying carrageenan. Before the administration of carrageenan, the mice are anaesthetized by i.p. injection of 0.5 mg/kg of medetomidine. The mice receive a 30 μL i.d. injection of carrageenan (1.5%, dissolved in normal saline) in one hind paw. The contralateral paw receive 30 μL of saline and it is used as a control. Paw volume is measured before and 3 h after the carrageenan injection with a plethysmometer. Oedema is expressed as a change in paw volume over time.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. MacKenzie SJ, et al. 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
[2]. Korhonen R, et al. 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]. Shalaby AM, et al. 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.