When modeling myeloablation cytostatic chemotherapy with cyclophosphamide in rats fulminant hyperammonemia was observed accompanied by an increase in the content of ammonia and glutamine, a decrease in the content of pyruvic and lactic acids in brain tissue. A positive correlation between the indicators of azotemia and the content of ammonia and glutamine in brain tissue was established. In loading test with ammonium acetate changes in the chemical composition of blood and brain tissue were more pronounced. The data obtained indicate the intensification of the intake of gastrointestinal ammonia into the brain from the blood, which leads to the depletion of the tissue pool of pyruvate with the introduction of cyclophosphane in doses used for myeloablation. Such changes create the conditions for disruption of energy supply of neurological functions during myeloablative cytotoxic chemotherapy using cyclophosphamide.

Toxicological characteristic of designer drugs from the group of synthetic opioids is presented. The historical aspects of illicit drug trafficking are considered. In the illicit drug market of EU countries 38 synthetic opioids, 22 of them belonging to fentanyl derivatives, have been revealed for the period 2005-2017. The widespread use of synthetic opioids among drug addicts has been accompanied by an increase in the number of fatal overdoses. In the United States the number of fatal poisonings by synthetic opioids of fentanyl series increased by 40.3 times between 1999 and 2017. The similar situation is emerging in other countries. This is due to the fact that the biological activity and toxicity of synthetic opioids far exceed those of morphine and heroin. The differences between the metabolism of heroin and synthetic opioids are considered. Data on the toxicity of synthetic opioids are presented. The neurotransmitter mechanisms of their respiratory depression, including disorders of opioid, GABAergic, glutamatergic and serotoninergic neurotransmitter systems are discussed. A brief description of the antidote activity of opioid receptor antagonists in acute poisoning by synthetic opioids is given.

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