Assessment of the toxic effect of 3-methylaminopropiophenone hydrochloride on the body

Abstract

Introduction. In modern medical practice, fluoxetine hydrochloride (prozac), referred to the group of highly effective antidepressants, is widely used for the treatment of mental disorders. In Russia, the domestic production of the drug with an economically feasible production technology has been managed. 
 In the synthesis of fluoxetine, the most important stage is the preparation of the main intermediate – 3-methylaminopropiophenone hydrochloride. Data on the toxic effect of this substance on the body in the open press, including in the international database PubChem, are not available.
 The research aim was the study on the toxic effect of 3-methylaminopropiophenone hydrochloride on the body of laboratory animals.
 Materials and methods. When studying the toxic effect of 3-methylaminopropiophenone hydrochloride in experiments on rats, the modes of single inhalation and subacute intragastric methods of exposure were reproduced. The effect of the substance on the condition of animals was assessed by the results of peripheral blood studies, biochemical blood serum parameters, morphological changes in internal organs including liver, kidneys, heart, stomach, pancreas and thyroid glands. Integral parameters were also used.
 Results. The results of the examination of animals subjected to acute inhalation intoxication and subacute intragastric exposure showed the same type of the changes in the peripheral blood and biochemical profile. The intake of 3-methylaminopropiophenone hydrochloride did not cause significant changes in the peripheral blood. The biochemical profile of the animals showed an increased activity of AST, ALT and alkaline phosphatase. In the blood serum of the primed rats, an increased content of total cholesterol, triglycerides and urea with a reduced content of protein and bilirubin was found. The impact of 3-methylaminopropiophenone hydrochloride at the morphological level revealed vascular disorders in all internal organs and moderately severe fatty degeneration of the liver and kidneys. In some parts of the liver, there was small-focus multi-lacular necrosis which covered groups of hepatocytes. 
 Limitations. The investigation is limited to the study on the toxicological characteristics of 3-methylaminopropiophenone hydrochloride. In accordance with the directive documents on the protection of experimental animals, the number of in vivo experiments is limited which is connected with the dangers of animals and with public ethical views on in vivo experiments.
 Conclusion. Different methods of intake of 3-methylaminopropiophenone hydrochloride under the conditions of acute inhalation and subacute intragastric experiments lead to a number of disorders of the hepatobiliary system with a negative impact on the common health status of the body. As an additional preventive measure to minimize the risk of acute and chronic intoxication in industries where contact with the substance is possible, including those involved in the synthesis of fluoxetine, an extended list of biochemical blood tests, ultrasound obsservation of the liver as part of periodic medical examinations of workers can be offered.