The object of this research is to study the pharmacological and toxicological properties of a widely abused class of drugs, the anthraquinone cathartics. Danthron and casanthranol are the prototypes to be investigated, in guinea pigs, mice, rats and humans. Though anthraquinones are absorbed from the gastrointestinal tract, and are capable of causing melanosis coli, colonic smooth muscle atrophy and myenteric plexus degeneration, published quantitative information about these drugs is almost non-existent. Therefore, we plan a detailed quantitative analysis of absorption, distribution, metabolism (both hepatic and intestinal bacterial), and elimination of the prototype anthraquinones. Correlated with this will be a quantitative study of the dose and time parameters necessary to produce melanosis, and colonic neuro- and myotoxicity. These pathological changes will be investigated by light, fluorescence and electron microscopy with the intention of clarifying the pathogenesis of these adverse effects, particularly in terms of the toxic principle(s), i.e., whether parent drug or metabolite. We will also determine if the cathartic and neurotoxic effects of anthraquinones vary with intake of vitamin C (ascorbic acid) or with preexisting diabetic enteric neuropathy. The very extensive use and misuse of this class of cathartic drugs creates a large potential for drug interactions and other risks in pregnant and nursing women, children and geriatric patients. The results of this study, providing fundamental pharmacological and toxicological information, should benefit physicians, patients, and federal regulatory agencies.
NIH ExPorter
NIH ExPorter