Pharmacology-based toxicity assessment of molsidomine and ATP-LONG combination with singular and repetitive injections under experimental conditions

Abstract

Abstract. The aim of the work was to study toxic properties of the new combined drug which comprise nitrovasodilator molsidomine and adenosine- 5’-triphosphate in a form of coordination compound with histidine, magnesium, and potassium (ATP-LONG). The drug was examined for its acute and subacute toxicity on Balb/c mice and Wistar rats of reproductive age with peroral (p/o) and sublingual (s/l) administrations. It has been established that LD50 of the substance contains over 10000 mg/kg (p/o) and 5010 mg/kg (s/l), which corresponds to the category of Practically non-toxic substances. The repetitive administrations within a 28 day period of the conditionally therapeutic dose of 260 mg/hg (s/l) did not cause any negative impact on physiological, biochemical, histological values in male and female rats. In doses 1300 and 2080 mg/kg, which exceed conditionally therapeutic doses by 5 and 8 times, the combination was not changing clinical laboratory urine and blood values but induced histological changes such as dilation and plethora of capillaries along with edema of smooth muscle cells of the brain, myocardium, liver, spleen, kidneys, and adrenal glands in rats. Additionally, the particular dosages of the combined substance provoked irritation of the mucous membrane of the tongue. Detected effects of the drug do not carry any pathological character and can be viewed as a specific reaction of the organism to high doses of nitrovasodilator. However, the duration and reversibility of unwanted consequences of molsidomine overdose, particularly in its combined form, need further investigation. Keywords: combination of molsidomine and ATP-LONG, acute and subacute toxicity