Abstract

Experimental allergic encephalomyelitis (EAE), a delayed hypersensitivity type of immunologic response, is considered a meaningful model for pharmacologic evaluation of drugs that are potentially useful in human autoimmune disease and organ transplantation. Cinanserin, an immunosuppressive agent and serotonin antagonist, represents a new class of compounds—both chemically and pharmacologically—which are effective in protecting Lewis-strain rats against EAE. Its protective effect was increased if treatment was postponed until several days prior to the onset of clinical symptoms, rather than being started prior to or concurrent with sensitization. In an attempt to delineate the mechanism responsible for the suppression of EAE by cinanserin, additional experiments employing pure antiserotonin or immunosuppressive analogs of cinanserin, various agents altering central nervous system levels of serotonin and several immunosuppressive drugs were carried out. The findings indicate that neither the immunosuppressive effect noted against humoral immunologic reactions nor a direct antagonism of serotonin are the only factors involved in the protection afforded by cinanserin against EAE.