Rolipram

Rolipram is a selective inhibitor of phosphodiesterases (PDE) IV^[1]. Rolipram increases intracellular cAMP and cGMP by inhibiting PDE, leading to an increase of norepinephrine, which suppresses expression of proinflammatory cytokines and other mediators of inflammation^[1]. Rolipram has potential clinical significance in alleviating endogenous depression and inflammation in the central nervous system^[1].

In vitro, Rolipram (10μM; 24h) significantly inhibited the basal adhesion of T lymphoblasts to ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1)^[2]. Rolipram (10μM; 1h) significantly inhibited lipopolysaccharide (LPS)-induced upregulation and secretion of TNF-α and IL-6 in cardiac fibroblasts^[3]. Rolipram (50nM; 24h) inhibited the expression of TGF‑β1 in hypertrophic fibroblasts^[4].

In vivo, Rolipram (10mg/kg; i.p.) with a single dose reduced the production of IL-1β, IL-5, IL-6 and TNF-α, while increasing the levels of IL-10 in C57BL/6 mice induced by lipopolysaccharide^[5]. Rolipram (1mg/kg; i.p.) acutely restored capillary perfusion in 18h in murine cecal ligation and puncture (CLP) C57BL/6 mice model^[6]. Rolipram (1.25mg/kg; 10d; i.p.) attenuated cognitive decline as well as anxiety- and depression-like behaviors in the triple-transgenic mice (3×Tg-AD) harboring 3 mutant genes APP_swe, Ps1_M146V and tau_P301L^[7].

References:

[1] hu J, Mix E, Winblad B. The antidepressant and antiinflammatory effects of rolipram in the central nervous system [J]. CNS drug reviews, 2001, 7(4): 387-398.

[2] Layseca-Espinosa E, Baranda L, Alvarado-Sánchez B, et al. Rolipram inhibits polarization and migration of human T lymphocytes [J]. The Journal of investigative dermatology, 2003, 121(1): 81-87.

[3] Ji J, Liu Z, Hong X, et al. Protective effects of rolipram on endotoxic cardiac dysfunction via inhibition of the inflammatory response in cardiac fibroblasts [J]. BMC cardiovascular disorders, 2020, 20(1): 242.

[4] Wu L, Xu L, Chen Y, et al. Rolipram plays an anti-fibrotic effect in ligamentum flavum fibroblasts by inhibiting the activation of ERK1/2 [J]. BMC musculoskeletal disorders, 2021, 22(1): 818.

[5] Lu X, Wang J, Chen X, et al. Rolipram protects mice from gram-negative bacterium Escherichia coli-induced inflammation and septic shock [J]. Scientific reports, 2020, 10(1): 175.

[6] Holthoff J H, Wang Z, Patil N K, et al. Rolipram improves renal perfusion and function during sepsis in the mouse [J]. The Journal of pharmacology and experimental therapeutics, 2013, 347(2): 357-364.

[7] Cong Y F, Liu F W, Xu L, et al. Rolipram ameliorates memory deficits and depression-like behavior in APP/PS1/tau triple transgenic mice: involvement of neuroinflammation and apoptosis via cAMP signaling [J]. The international journal of neuropsychopharmacology, 2023, 26(9): 585-598.