Кафедра фармакології

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Перегляд Кафедра фармакології за Ключові слова "2-oxoindoline"

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    Встановлення токсичності 2-гідрокси-n-нафтален-1-іл-2-(2-окси-1,2-дигідроіндол-3-іліден)-ацетаміду
    (Вищий державний навчальний заклад України «Українська медична стоматологічна академія», 2017) Луценко, Руслан Володимирович; Луценко, Руслан Владимирович; Lutsenko, R. V.
    На 100 мишах вивчали токсичність похідного 2-оксоіндоліну при внутрішньоочеревинному і ентеральному уведенні. Встановлено, що максимальна толерантна доза сполуки дорівнювала 1500 мг/кг, найменша смертельна доза (LD16) становила 1920 мг/кг, а LD100= 4500 мг/кг. При цьому LD50 речовини складала 3250±159 мг/кг. Довірчі межі величини LD50 становили 3250 (2890,7ч3609,3) мг/кг. При ентеральному введенні LD50 складала більше 3000 мг/кг. Згідно класифікації К.К. Сидорова та ГОСТу 12.1.007-76 сполука належить до VI класу токсичності, тобто відносно нешкідлива. Сполука є менш токсичним за діазепам (у 88 разів) і перевищує його у 14,8 разу за показником відносного терапевтичного індексу. The identification of toxicity of 2-hydroksy-n-naftalen-1-il-2-(2-oksi-1,2-dyhidroindole-3-iliden)-acetamideНа 100 мышах изучали токсичность производного 2-оксоиндолина при внутрибрюшинном и энтеральном введении. Показано, что максимальная толерантная доза соединения равна 1500 мг/кг, наименьшая смертельная доза (LD16) составляла 1920 мг/кг, а LD100 = 4500 мг/кг. При этом LD50 вещества была на уровне 3250±159 мг/кг. Доверительные пределы величины LD50 равнялись 3250 (2890,7 ч 3609,3) мг/кг. При энтеральном введении LD50 составляла более 3000 мг/кг. По классификации К.К. Сидорова и ГОСТа 12.1. 007-76 соединение относится к VI классу токсичности, то есть относительно безвредно. Вещество менее токсично чем диазепам (в 88 раз) и превышает его в 14,8 раз по значению относительного терапевтического индекса. Abstract. Modern psychiatry and neurology requires the development of new methods and means with difficult spectrum of psychotropic action. It can avoid polypragmasy and it can affect different areas of the pathogenesis of mental disorders. So, the search and the development of new drugs in psychotropic spectrum are actual and it can possess cerebral and protective peculiarities. Ethers and amides of 2-oksoindolin-3-glyoxalic acid are prospective and they require the examination.The aim of the paper is to identify acute toxicity of 2-hydroksy-N-naftalen -1-il -2-(2-oksi-1,2-dyhidroindole-3-iliden)-acetamide (Substance 18) at intraperitoneal administration and the intake inside. Object and methods. Experiments were done on 100 non-linear mice with body weight 18-20 gr. Acute toxicity was studied in 2-hydroksy-N-naftalen -1-il -2-(2-oksi-1,2-dyhidroindole-3-iliden)-acetamide on mice. The range of doses at intraperitoneal administration was (1500, 2000, 2500; 3000, 3500, 4000, 4500 mg/kg). The substance was administered orally in such doses as 2000, 2500 and 3000 mg/kg. Median lethal dose of the substance was defined by Cr. Karber method.Results and their discussions. The signs of acute poisoning were detected during experiments. The first symptoms of intoxication occurred in 5-10 minutes after intraperitoneal administration of the substance. Animals’ death occurred in some hours after overdosage as usual during 12-24 hours. In the next period animals’ death was not observed. Clinical picture of intoxication was characterized by inhibition, adynamia, areflexia, and lateral position of the trunk. The death was from respiratory arrest. It was determined that maximal tolerable dose of the substance of derivatives of 2-oksoindoline was equal to 1500 mg/kg, the least lethal dose was (LD16) 1920 mg/kg, а LD100= 4500 mg/kg. It was determined that the substance LD50 was 3250±159 mg/kg. Confidence bounds of LD50 was 3250 (2890,7ч3609,3) mg/kg. During examination of oral administration of the substance in the dosage 3000 mg/kg cases of acute lethality of mice have not been observed during the first day and during 5 days of the examination. Subsequent increase in doses was complicated by the lack of solubility of the compounds and standards that limit the administration into the stomach of the volume of the liquid. Symptoms of poisoning were observed after 10-15 minutes and they were not significantly expressed and they were characterized by common inhibition. Clinic poisoning lasted 3-4 hours, and then gradually decreased. The general condition was restored in 4-7 hours. Thus, LD50 of compound 18 in mice was 3250±159 mg/kg at oral administration more than 3,000 mg/kg. According to the classification of K.K. Sidorova and GOST 12.1.007-76 the substance (LD50 > 3250 mg/kg) is a substance of 6th class of toxicity that is relatively harmless. It has established, the substance is less toxic than diazepam (in 88 times) and increases the drug of comparison in 14.8 times based on the relative therapeutic index.Conclusions. Median lethal dose of 2-hydroksy-N-naftalen-1-il-2-(2-oksi-1,2-dyhid-roindole-3-iliden) acetamide at intraperitoneal administration by mice was 3250±159 mg/kg and it refers to the 6th class of toxicity. LD50 is equal to 3000 mg/kg during oral administration. Toxicity of the substance is significantly lower than in diazepam.