CHEMICAL CHARACTERIZATION AND COMPARATIVE CELLULAR EFFECTS OF META-IODOBENZYL GUANIDINE AND BENZYL GUANIDINE

meta-Iodobenzyl guanidine (MIBG) combines the structural properties of the neuron-blocking agents bretylium and guanethidine and is being us ed increasingly for various clinical applications. Different samples o f MIBG were assayed for possible contamination with benzyl guanidine ( BG). Fast-atom-bombardment mass spectrometry (FAB-MS) analysis showed a prominent but variable m/z 150 signal, corresponding to a protonated BG. The MS/MS fragmentation pattern of these [M + H](+) ions was simi lar to that obtained from FAB-MS-generated, protonated BG, confirming the proposed molecule and associated structures. RP-HPLC analysis of b oth guanidines, however, excluded the possibility of contamination of MIBG with BG. It was therefore concluded that the BG signal was an art ifact of the FAB-MS procedure. In addition, the importance of the meta -substituted iodine for the biological activity of MIBG was investigat ed. Three different biochemical and cell-biological properties of MIBG were compared with those of its precursor MIBA and BG. The assays use d were: inhibition of the catecholamine ''Uptake I'' system in SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells, inhibition of mitocho ndrial respiration, and general cytotoxicity in L1210 leukemia cells. Of the drugs tested, MIBG was the most efficient in Uptake I inhibitio n and was more toxic in survival assays, but as compared with BG it wa s almost equipotent in inhibiting mitochondrial respiration. These fin dings contribute to a further elucidation of the mechanism by which MI BG exerts its various actions.