Open AccessA TWO-YEAR STUDY OF CANCEROGENIC POTENTIAL OF THE NEW OPIOID RECEPTOR ANTAGONIST ONDELOPRAN IN RATS
Author(s) -
Kirill Kryshen,
А. А. Мужикян,
Д С Гайдай,
К. О. Заикин,
A.E. Katelnikova,
М. Ю. Самсонов,
Э. И. Мухаметшина,
Г. Е. Коноплева,
Elena Shipaeva,
Алия Ануарбековна Дмитриева,
Ф. Ш. Шагиахметов,
А. О. Попова,
М.Н. Макарова,
Валерий Геннадьевич Макаров
Publication year - 2019
Publication title -
issledovaniâ i praktika v medicine
Language(s) - English
Resource type - Journals
eISSN - 2410-1893
pISSN - 2409-2231
DOI - 10.17709/2409-2231-2019-6-2-6
Subject(s) - placebo , antagonist , medicine , opioid , naltrexone , receptor antagonist , pathological , opioid receptor , pharmacology , opioid antagonist , receptor , physiology , pathology , (+) naloxone , alternative medicine
Opioid receptor antagonists are widely used for the treatment of alcohol dependence. Currently, original drug Odelepran (INN: ondelopran) with a unique binding pro le to all three types of human opioid receptors (μ, κ, δ) is being developed by R-Pharm. Aim of the study. To investigate a cancerogenic poten
al of the new opioid receptor antagonist ondelopran in a twoyear study in rats Materials and methods. The study cancerogenic potencial was performed in male and female Wistar rats at the age of 8–10 weeks at the start of experiment. All animals were allocated to 8 groups. Each group consisted of 50 animals of each sex. Test item (ondelopran lm-coated tablets, 125 mg), was administered to the animals intragastrically as a tablets suspension in 1% starch solution daily, 5 days a week for 24 months in two doses: 10 mg/kg (equivalent therapeutic dose for humans) and 100 mg/kg. Animals of control groups were administered with placebo and vehicle (1% starch solution). Clinical observation and examination of animals were conducted weekly to detect any signs of intoxication; dynamics of the body weight and registration of animal deaths were also assessed. To assess the rate of the pathological changes, the macro- and microscopic examina
on of inner organs and neoplasms was conducted. Results. During the study the mortality rates did not di er between the groups. Clinical signs ts.and symptoms of intoxication upon administration of the tested item and placebo were not observed. Neoplasms were found in the organs of all groups of animals. More than 30 variants of neoplasms were identi ed upon pathomorphological examination. The identi ed tumors are typical for rats and considered as spontaneous age-related pathology. There was no statistically signi cant di erences between groups in the total incidence of tumors. Conclusion . To conclude the above said, the test item of the ondelopran lm-coated tablets, 125 mg have no carcinogenic properties.