Cytotoxic effects of monodansylcadaverine and methylamine in primary cultures of rat cerebellar neurons

The effects of dansylcadaverine and methylamine, competitive inhibitors of transglutaminase, were examined in primary cultures of dissociated rat cerebellar neurons. Addition of the drugs at plating time resulted 24 hr later in irreversible cytotoxic effects evidenced by failure of aggregation and neurite formation. Cytotoxicity was dose-dependent with methylamine being more potent (IC50 = 20 microM) than dansylcadaverine (IC50 = 30 microM). The cytotoxic effects were less potent when drugs were added 24 hr after plating, the time when neurons had already begun to extend neurites. Drugs were effective in the various sera and heat-inactivated sera tested. We concluded that low doses of methylamine and dansylcadaverine have potent toxic effects on primary neuronal cultures.