NON-PEPTIDE INHIBITION OF T-LYMPHOCYTE ACTIVATION AND THERAPIES RELATED THERETO

摘要

Compounds, preparations and methods for immunosuppressive treatment of autoimmune disorders, graft rejection and/or graft/host disease. Therapeutically effective amounts of certain substituted triarylmethane compounds, such as 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole, are administered to mammalian patients to selectively inhibit the calcium-activated K<+> channel (IKCa1) in Lymphocytes, monocytes, macrophages, platelets or endothelial cells without concomitant inhibition of P450-dependent enzyme systems, resulting in reduction of antigen-,cytokine-, or mitogen-induced calcium entry through store operated calcium channels in these cells, suppression of cytokine production by these cells, and inhibition of activation of these cells. Such inhibition of the Ca<++> activated K<+> channel (IKCa1) prevents the pre-Ca<++> stage of cell activation and thus causes immunosuppression and an anti-inflammatory response.