Rolipram

Rolipram is a PDE4 inhibitor, with blood-brain barrier permeability, that reverses β-amyloid-induced learning and memory impairment in rats. Rolipram elevates intracellular cAMP and clevels and regulates the cAMP/CREB signaling pathway, thereby alleviating neuroinflammation and apoptotic responses. Rolipram promotes neuronal differentiation of human bone marrow mesenchymal stem cells and inhibits Methamphetamine- and morphine-induced hyperlocomotion in mice. Rolipram also reduces the viability of glioblastoma stem-like cells and enhances Bevacizumab (HY-P9906)-induced cell death. Rolipram inhibits the expression of proinflammatory cytokines and enhances central noradrenergic transmission. Rolipram is mainly used in studies related to various central nervous system diseases including Alzheimer's disease, major depressive disorder, glioblastoma multiforme, and multiple sclerosis^{[1][2][3][4][5]}. IC50 & Target:IC50: 3 nM (PDE4A), 130 nM (PDE4B), 240 nM (PDE4D)^[1] In Vitro:Rolipram (0.5-25 μM; 6-24 h) upregulates the expression of neural precursor cell genes in hBM-MSCs in a dose- and time-dependent manner, with the maximal effect observed at 1 μM for 12 h^[2].
Rolipram (1-25 μM; 12 h) shows no toxicity to hBM-MSCs at concentrations ≤5 μM, but induces significant cytotoxicity at 10 μM and 25 μM^[2].
Rolipram (1 μM; 12 h) significantly increases the neuronal differentiation rate, neurite length, and neurite number of hBM-MSCs following neuronal induction^[2].
Rolipram (1 μM; 12 h) enhances neuron-specific gene expression and suppresses non-neuronal lineage gene expression in hBM-MSCs following neuronal induction^[2].
Treatment with Rolipram (10 μM; 48 h) alone reduces the viability of CD133+/CD15+ human glioma stem cells (T2), and its cytotoxic effect is stronger when used in combination with bevacizumab than when either drug is used alone^[4].
Rolipram downregulates antigen-driven proliferation and the gene expression of IL-5 and IFN-γ in human peripheral blood mononuclear cells, but does not affect the gene expression of IL-4^[5]. In Vivo:Rolipram (0.1-0.5 mg/kg; i.p.; once daily; 24 days) dose-dependently reverses Aβ25-35-induced learning and long-term memory deficits in rats, alongside reversing associated hippocampal reductions in pCREB and Bcl-2, and increases in NF-κB p65 and Bax^[1].
Rolipram (0.5 mg/kg; i.p.; once daily; 14 days) reverses Aβ1-42-induced hippocampal changes in pCREB, NF-κB p65, Bcl-2, and Bax in rats, confirming effects observed with Aβ25-35^[1].
Rolipram (1.0-10 mg/kg; i.p.; single dose; 15 minutes pre-methamphetamine) significantly suppresses methamphetamine-induced hyperlocomotion in male ddY mice, with 10 mg/kg producing nearly complete inhibition^[3].
Rolipram (10-100 mg/kg/day; p.o.; daily; 5-14 days) induces dose-dependent toxic effects in female rats, including cardiac, vascular, gastrointestinal, and salivary gland changes, with lethal effects at 100 mg/kg/day within 5 days^[5].
Rolipram (0.02-400 mg/kg; systemic; single dose) induces a characteristic behavioral syndrome and mild hypothermia in rats, with effects linked to enhanced central adrenergic signal transduction^[5].