RETENTION MECHANISM OF IMIDAZOLES IN CONNECTIVE-TISSUE - II - ACTIVATION OF IMIDAZOLES IN CUPRO-ASCORBATE SYSTEM FOR IRREVERSIBLE BINDING FORMATION WITH AORTIC TISSUE IN-VITRO

In order to obtain an insight into the retention mechanism of drugs wi th imidazole moiety in the connective tissue, the in vitro characteris tics of the interaction between C-14-labeled imidazoles (imidazole and its 2-methyl derivative) and slices of dog aorta were studied. We fou nd that cupro-ascorbate-catalyzed oxidative reactions for the imidazol es led to their irreversible binding with connective tissue, and that, from a study using protein modifiers, the aldehydic function intrinsi c to the tissue protein was involved in the binding formation. This ch aracteristic in vitro was observed under physiological conditions, hen ce it can be extrapolated to the in vivo situation and could also give a clue to the nature of the retention of imidazole-containing drugs i n connective tissue.