The influence of Notrombel on the process of photoinduced thrombogenesis
Objectives. Our objectives were to study the effect of Notrombel administration (one of the representatives of a new class of compounds, N, N'-substituted piperazines) on the development of experimental thrombosis. Material and methods. Thrombosis of the femoral artery was induced in Wistar male rats by 30-minute laser irradiation (532 nm, 60 mW, irradiation area - 1 mm2) after intravenous injection of Rose Bengal A (17 mg/kg). The blood flow was recorded by high-frequency ultrasonic dopplerography (20 MHz) before irradiation and every 10 minutes after irradiation. Notrombel and Acetylsalicylic Acid (ASA) were administered intravenously (control - 0.9 % sodium chloride) and intragastrically (control - water) in increasing doses. Results. Thrombosis of the femoral artery developed in all control animals during 30-minute laser irradiation. With a single intravenous administration, Notrombel was more effective than ASA (100 % prevention of thrombosis at doses of 0.0045 mM/kg and 0.05 mM/kg, respectively). The calculated effective dose (ED50) for Notrombel was about 0.0021 mM/kg, and for ASA - 0.029 mM/kg. After seven intravenous administrations of Notrombel, no cumulative effect was observed (a single dose ED50 = 0.0021 mM/kg), in contrast to ASA (ED50 = 0.0032 mM/kg). After seven intragastric injections, the antithrombotic activity of the drugs was close (for Notrombel ED50 = 0.0049 mM/kg, for ASA 0.0041 mM/kg). Conclusions. With a single intravenous injection, the antithrombotic activity of Notrombel (ED50 = 0.0021 mM/kg) is higher than that of ASA (ED50 = 0.029 mM/kg). With the course of intragastric and intravenous administration, the effects of the drugs are comparable. Unlike ASA, Notrombel had no cumulative effect, which indicates the safety of repeated parenteral administrations of the drug.