Rimonabant (SR141716) is the first selective cannabinoid receptor CB₁ antagonist described. Along with its anti‐obesity action, emerging findings show potential anti‐proliferative and anti‐inflammatory action of SR141716 in several in vitro and in vivo models. In this study we have investigated the anti‐proliferative and immunomodulatory effects of SR141716 in human peripheral blood mononuclear cells (PBMCs).

We have evaluated in vitro the effect of SR141716 in human PBMCs stimulated with different mitogens. Cell proliferation was assessed by ³H‐thymidine incorporation. Cell cycle, cell death and apoptosis were analysed by flow cytometry. Protein expression was investigated by Western blot.

SR141716 significantly inhibited the proliferative response of PBMCs and this effect was accompanied by block of G₁/S phase of the cell cycle without induction of apoptosis and cell death. SR141716 used in combination with 2‐methyl‐arachidonyl‐2′‐fluoro‐ethylamide (Met‐F‐AEA), a stable analogue of the endogenous cannabinoid anandamide, showed synergism rather than antagonism of the inhibition of cell proliferation. The immunomodulatory effects of SR141716 were associated with increased expression of IκB, phosphorylated AKT (p‐AKT) and decreased expression of NF‐κB, p‐IκB, p‐ERK, COX‐2 and iNOS.

Our findings suggest SR141716 is a novel immunomodulatory drug with anti‐inflammatory properties.

British Journal of Pharmacology (2008) 153, 1003–1010; doi:10.1038/sj.bjp.0707651; published online 24 December 2007