PMS-601: a new PAF-receptor antagonist with antiretroviral and anti-inflammatory properties.

The platelet-activating factor (PAF) plays a major role in neuropathogenesi s associated with human immunodeficiency virus (HIV) infection by enhancing the inflammatory syndrome and viral replication, particularly in cells of the macrophage lineage, and its neurotoxic properties. We therefore evaluat ed the ability of PAF-R antagonists to inhibit HIV-1 replication and down-m odulate the synthesis of pro-inflammatory mediators in healthy or HIV-1-inf ected macrophages. PMS-601 demonstrated the highest anti-HIV activity Consi dering ifs mode of action and anti-inflammatory properties, PMS-601 interfe res with early and late steps of the HIV biological cycle and decreases the synthesis of PAF; TNF-alpha, MIP-1 alpha; MIP-1 beta and RANTES. Altogethe r; these results suggest that PAF-receptor antagonists, and particularly PM S-601, could be of potential value as treatment adjuvants in HIV infection. (C) 2000 Editions scientifiques et medicales Elsevier SAS.