The effect of Notrombel on FeCl3-induced carotid artery thrombosis in rats

Abstract

Aim. To study the effect of Notrombel (ZAO Vertex, St. Petersburg, Russia), a drug of the N, N’-substituted piperazine class containing a carboximidamide group, on experimental thrombosis. Methods. Experiments were carried out on male Wistar rats weighing 250-270 g. Notrombel was administered intravenously and intragastrically for 10 days (course doses 25, 50, and 100 mg/kg). Acetylsalicylic acid (ASA) and Сlopidogrel (course doses 10.5 and 20 mg/kg, respectively) were used as comparator drugs. Carotid artery thrombosis was induced by a 60-s application of 20% FeCl₃. Blood flow was recorded by high-frequency ultrasonic dopplerography (Minimax-Doppler-K, St. Petersburg, RF; sensor operating frequency, 20 MHz). Stagnation of blood flow was considered as an indicator of carotid artery occlusion. Results. In control rats 20-30 minutes after the application of FeCl3, the carotid blood flow was undeterminable, which indicated development of thrombosis. Notrombel, both intragastric and intravenous, inhibited the development of FeCl₃-induced carotid thrombosis. The most effective dose was 100 mg/kg irrespective of the administration route. Thrombosis has not developed in any experiment. The antithrombotic effect of Notrombel was comparable to that of ASA and Clopidogrel. The Notrombel inhibition of platelet activity and its antioxidant properties contribute to the mechanism of Notrombel antithrombotic effect. Conclusion: Notrombel can be considered as a promising antithrombotic drug.