Metabolism and kinetics of renal elimination of N-picolyl-3,5-dimethylbenzamides

Abstract

The metabolism and kinetics of renal elimination of N-(2-picolyl)-, N-(3-picolyl)- and N-(4-picolyl)-3,5-dimethylbenzamides were studied. These products have a depressive activity on the central nervous system, as well as an anti-inflammatory and spasmolytic activity. The elimination of the products N-(3-picolyl)- and N-(4-picolyl)-3,5-dimethylbenzamides includes a process of metabolic oxidization of the atom of pyridinic nitrogen with formation of the corresponding N-oxides as main products of its bio-transformation. The process of N-oxidization was not observed with the product N-(2-picolyl)-3,5-dimethyl-benzamide. The results showed that the renal elimination rate of the products studied is greater as the pyridinic nitrogen moves away from the amide group. In the biotransformation process of these products, there is an opposite effect, i.e., the formation of corresponding N-oxides is lower as the pyridinic nitrogen approaches the amide group.