Physical and chemical criteria for hazard assessment of CNS-active xenobiotics

Introduction . Forensic medical examinations frequently encounter poorly understood, potentially hazardous psychoactive substances. At the same time, information on the biological activity of such substances may be either fragmentary and contradictory or absent altogether. Therefore, the development of approaches to predicting the health hazard of xenobiotics is an urgent task of emergency medicine. Objective. To study the relationship between physicochemical properties and the hazard rate of one class of CNS-active substances using the methods of mathematical analysis followed by scientific substantiation of criteria for preliminary hazard assessment of narcotic drugs. Ма terials and methods . The study models included the known structures of narcotic analgesics, divided into three groups according to their potential hazard rate. The physicochemical properties of such substances, i.e., molecular weight, polarity, polar surface area, distribution coefficients, and basic dissociation constants were considered as potential hazard factors. Linear discriminant analysis was used to identify the relationship between the physicochemical properties of psychoactive substances and their hazard potential. Results. The considered example of one class of CNS-active substances confirms the relationship between their hazard rate and the physicochemical properties affecting their redistribution from the central bloodstream to the central nervous system. Physicochemical criteria for predicting the hazard rate of psychoactive substances are proposed. These criteria serve as classification functions that distinguish groups of model substances. Conclusions. The physicochemical properties of psychoactive substances and the strength of their binding to target receptors equally determine the characteristics of their toxic effect. The formulated classification functions, calculated based on the physicochemical properties of substances, can be used for a preliminary hazard assessment of xenobiotics during their detection in biological samples.