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 used increasingly for various clinical applications. Different samples of 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 similar to that obtained from FAB-MS-generated, protonated BG, confirming the proposed molecule and associated structures. RP-HPLC analysis of both guanidines, however, excluded the possibility of contamination of MIBG with BG. It was therefore concluded that the BG signal was an artifact of the FAB-MS procedure. In addition, the importance of the meta-substituted iodine for the biological activity of MIBG was investigated. Three different biochemical and cell-biological properties of MIBG were compared with those of its precursor MIBA and BG. The assays used were: inhibition of the catecholamine "Uptake I" system in SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells, inhibition of mitochondrial respiration, and general cytotoxicity in L1210 leukemia cells. Of the drugs tested, MIBG was the most efficient in Uptake I inhibition and was more toxic in survival assays, but as compared with BG it was almost equipotent in inhibiting mitochondrial respiration. These findings contribute to a further elucidation of the mechanism by which MIBG exerts its various actions.
Van den Berg
J D
JD
Department of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis, Amsterdam.
Smets
L A
LA
Rutgers
M
M
Grummels
A
A
Fokkens
R
R
Jonkergouw
P
P
van Rooij
H
H
D019797:3-Iodobenzylguanidine; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006146:Guanidines / Q000737:chemistry* / Q000494:pharmacology*; D007457:Iodine Radioisotopes / Q000737:chemistry* / Q000494:pharmacology*; D007462:Iodobenzenes / Q000737:chemistry* / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000970:Antineoplastic Agents; D002395:Catecholamines; D006146:Guanidines; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D019797:3-Iodobenzylguanidine