The effect of histamine type 2 receptor antagonists on human immunodeficiency virus (HIV) replication: identification of a new class of antiviral agents.

The suppression of human immunodeficiency virus (HIV) replication by histamine type 2 (H2) receptor antagonists, cimetidine, ranitidine, and famotidine was examined in vitro. The 50% reduction (IC50) in p24 antigen expression caused by the anti-ulcer agent, cimetidine, was observed at 26.8 nM with IC100 at 10 microM. Unlike azidothymidine-a reverse transcriptase inhibitor-cimetidine blocked HIV infection without affecting cell growth, as no cytotoxicity was observed even at the highest 1 mM dose. Ranitidine and famotidine were less potent than cimetidine. H1 antagonists, cyproheptadine and diphenhydramine, had no effect on HIV replication. Although the activity of cimetidine was observed at concentrations attainable by oral administration, the mechanism of anti-HIV action is unknown. This is the first report on antiretroviral action of H2 blockers. Further studies are warranted to establish the potential of a new class of anti-HIV agents with immunomodulating properties.