The importance of the interaction of drug molecules with membranes is discussed. The first two examples use the interaction of benzylpyrimidines with membranes of sensitive and resistant E. coli. This leads to a partial inactivation due to binding and to a change in mechanism of action, respectively. Another example deals with the interaction of amphiphilic benzylamines with artificial bilayers which lead to a change in conformation. The neuroleptic activity of Flupirtin derivatives could be described by the degree of interaction with bilayers quantified by NMR technique and a newly developed HPLC technique. Finally the interaction of amphiphilic drugs with membranes, possibly responsible for reversal of multidrug resistance in tumor and malaria therapy, is discussed.

Environmental factors have been implicated in the pathogenesis of neurodegenerative diseases. Maneb (MB) and mancozeb (MZ) have been extensively used as pesticides. Exposure to MB lowers the threshold for dopaminergic damage triggered by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. MB and MZ potentiate 1-methyl-4-phenylpyridium (MPP(+))-induced cytotoxicity in rat pheochromocytoma (PC12) cells partially via nuclear factor kappa B (NF-κB) activation. RTP801 dramatically increased by oxidative stresses and DNA damage is the possible mechanism of neurotoxins-induced cell death in many studies. This study demonstrated that MB and MZ induced DNA damage as seen in comet assay. The expressions of RTP801 protein and mRNA were elevated after MB and MZ exposures. By knocking down RTP801 using shRNA, we demonstrated that NF-κB activation by MB and MZ was regulated by RTP801 and cell death triggered by MB and MZ was associated with RTP801 elevation. This revealed that the toxic mechanisms of dithiocarbamates are via the cross talk between RTP801 and NF-κB.