The aim of the study is to summarize the histology and morphometry of cortical neurons in acute clozapine and ethanol poisoning.Material and methods. Histological examination of the parietal cortical brain samples of 26 patients died during the Day 1 of acute clozapine and ethanol poisoning (23 males and 3 females aged 22-63 years) was performed. The blood ethanol level was 1.4-4.1%o. The level of clozapine in the blood ranged between 0.24 and 5.8 mg%, in the liver between 0.097 and 6.5 mg%, in kidneys between 0.03 and 3.5 mg%. The cortical samples for morphometric examination were placed in 10% neutral paraformaldehyde, the histological sections were done and stained with hematoxylin and eosin, as well as according to Niessl. The morphological analysis was performed using the video light microscopy. The number of damaged neurons (with separate quantification of reversible, intermediate, and irreversible damage) was assessed. The statistical analysis was done using the non-parametric methods.Results. The signs of brain neuronal damage in acute clozapine and ethanol poisoning, as well as forensic chemical tests, might be used for establishing the direct cause of death.

Клозапин-атипичное антипсихотическое средство с доказанной эффективностью, которое широко используется в клинической практике. Однако, его применение сопряжено с высоким риском развития серьезных побочных эффектов. Угрожающие жизни состояния при приеме клозапина могут быть следствием идиосинкразии, острого отравления в результате непреднамеренной передозировки назначенного препарата, суицидального поведения, криминальных действий. В обзоре представили современные данные о механизмах терапевтического и токсического действия клозапина. Описали воздействие клозапина на клеточные рецепторы и ультраклеточные структуры. Рассмотрели роль основных и промежуточных метаболитов данного лекарственного средства в развитии токсических эффектов. Ключевые слова: клозапин; лекарственный метаболизм; острые отравления; кардиотоксичность; агранулоцитоз; клозапин-индуцированый миокардит Clozapine is an atypical antipsychotic agent with a confirmed effectiveness which is widely used in the clinical practice. However, its administration is associated with a high risk of serious adverse events. Life-threatening conditions related to administration of clozapine may be a result of idiosyncrasy, acute poisoning resulting from unintentional overdose of the prescribed dug, suicidal behavior, and criminal actions. The review presents current data on the mechanism of therapeutic and toxic effect of clozapine. It describes the effect of clozapine on cell receptors and ultracellular structures. It dwells on the contribution of major and intermediate metabolites of this medicinal agent to the development of toxic effects.

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