BIOLOGICAL ACTIVITY OF DIAZONIUM COMPOUNDS (II): POSITIVE INO- AND CHRONOTROPIC ACTIONS ON GUINEA PIG ATRIA OF 4 (OR 5)-DIAZO-IMIDAZOLE-5 (OR 4)-CARBOXAMIDE

Abstract

Diazonium compounds have been employed extensively to modify proteins (1-6), to study the composition and structure of enzymes and their relationships to enzyme activity (7-10), and also to produce specific antigenic determinants (11). However, these compounds have restricted interest in their use because of their lack of specificity in formation of different azo derivatives of amino acids, and because of the difficulty of obtaining them in crystalline form. Only a few investigations have been reported on pharmacological activities of diazonium compounds (12-18). During our studies on the antitumor and antibacterial activities of 4(or 5)-aminoimidazole-5(or 4)-carboxamide (a precursor of purine nucleotides) derivatives (12-14), the diazonium compound, 4(or 5)-diazoimidazole-5(or 4)-carboxamide (Diazo-ICA) was found to act as a central depressant in experimental animals (16, 17). It was reported that the diazonium group of Diazo-ICA played an important role in these biological activities (12-14, 16-17). Therefore, it was of interest to obtain detailed information on the pharmacological properties of Diazo-ICA. The present paper reports positive ino- and chronotropic effects of Diazo-ICA on isolated guinea pig atrium caused by its interaction with certain sulfhydryl groups in the tissues. It was also found that these effects of the diazonium compound on the isolated atria seemed to be partially mediated by release of catecholamine from the tissues.