Distribution of methyl and isopropyl N-methylanthranilates and their metabolites in organs of rats treated with these two essential-oil constituents.

Two volatile alkaloids, methyl (MMA) and isopropyl N -methylanthranilates (IMA), identified in the essential oil of Choisya ternata Kunth (Rutaceae), have been proven to possess polypharmacological properties (antinociceptive, anti-inflammatory, gastro-, hepato-, nephroprotective activities, anxiolytic and antidepressant properties, and likewise an effect on diazepam-induced sleep). In the continuation of our investigation of their urinary-metabolite profiles, we performed GC-MS analyses of the diethyl-ether extracts of selected tissues (liver, kidneys, heart, brain, lungs, quadriceps femoris muscle, and spleen) of rats intraperitoneally treated with MMA or IMA (2 g kg−1). Organ-metabolite profiles of MMA and IMA were qualitatively mutually analogous (varying only in the alcohol moiety of the metabolites), and generally analogous to their urinary-metabolite profiles. The greatest diversity and the highest overall amount of anthranilate metabolites was found in the hepatic tissue. The principal anthranilate-related compounds in the organs of rats treated with MMA, among 12 detected, were the products of ester hydrolysis, N -methylanthranilic and anthranilic acids. In the tissues of IMA-treated rats, among 16 compounds, the most abundant ones were the unmetabolized IMA and N -methylanthranilic acid. A collection of the compositional data regarding the anthranilate-related metabolites was statistically treated by multivariate statistical analysis that provided a better insight into the possible biotransformation pathways. Image 1 • Metabolism of methyl (MMA) and isopropyl N -methylanthranilates (IMA) was investigated. • GC-MS analyses of the Et 2 O extracts of the homogenates of the chosen tissues of MMA/IMA-treated rats were performed. • Organ-metabolite profiles of MMA and IMA were qualitatively analogous and analogous to their urinary-metabolite profiles. • Products of ester group hydrolysis and the unmetabolized compounds were the major anthranilates detected in the organs. • Multivariate statistical analysis pinpointed to specific connections between the analyzed xenobiotic metabolites. [ABSTRACT FROM AUTHOR]