Antiplatelet and Antithrombotic Properties of Compound L-36, a 6H-1,3,4-Thiadiazine Derivative.

Compound L-36, a new derivative of 6H-1,3,4-thiadiazine, was studied in in vitro and in vivo experiments. This compound exhibits high antiplatelet and antithrombogenic activity. In in vitro experiments, compound L-36 by its antiplatelet activity (by IC50) was superior to acetylsalicylic acid by 9.4 times. In in vivo experiments, compound L-36 by its ED50 value was close to the comparison drug. On the model of pulmonary artery thrombosis, compound L-36 ensured better survival of experimental animals than acetylsalicylic acid. Morphological studies showed that compound L-36 effectively attenuated the thrombosis processes in the pulmonary tissue induced by intravenous injection of a thrombogenic mixture (epinephrine and collagen).

Antiplatelet Activity of Riamilovir under Conditions of Lipopolysaccharide Intoxication.

We studied the effect of antiviral agent riamilovir on ADP-induced platelet aggregation in the absence and presence of LPS. Unlike acetylsalicylic acid (reference drug), riamilovir did not exhibit antiplatelet effect in vitro. However, it markedly suppressed platelet reactivity in LPS-treated blood samples and was 2.2-fold superior to acetylsalicylic acid in terms of IC50 value. In in vivo experiments, riamilovir under conditions of hypercytokinemia blocked platelet aggregation in rats by 64%.

Antithrombotic Activity of the Antiplatelet Agent Angipur on the Model of Arterial Thrombosis in Rats with Isoproterenol-Induced Myocardial Infarction.

We studied the effect of Angipur on the process of experimental thrombosis induced by damage to the carotid artery wall by surface application of 50% ferric chloride (III) solution in rats without comorbidities and with isoproterenol-induced myocardial infarction. In animals without comorbidities, Angipur administered intravenously was 1.2 times less effective, in terms of ED50, than the well-known inhibitor of GPIIb/IIIa platelet receptors tirofiban. However, under conditions of non-coronary myocardial infarction, Angipur significantly prolonged the time of thrombus formation and exhibited 1.4-fold higher activity than the reference drug tirofiban.

Antithrombotic Activity of a Novel Diazepino[1,2-α] Benzimidazole Derivative on Arterial Thrombosis Model in Rats without Concomitant Pathology and in Rats with Experimental Myocardial Infarction.

Antithrombotic activity of a novel tricyclic derivative of diazepino[1,2-α]benzimidazole (DAB-15) was examined on the model of arterial thrombosis developed in rats without concomitant pathology and in rats with experimental myocardial infarction. DAB-15 demonstrated high antithrombotic efficacy in modeled thrombosis of carotid artery in rats without the concomitant pathology surpassing that of the reference drugs acetylsalicylic acid and clopidogrel by 5.1 and 4.8 times, respectively. In rats with experimental noncoronary myocardial infarction, DAB-15 increased the thrombus formation time by 86.2% in comparison with experimental control level in non-treated rats with similar myocardial infarction.

Antithrombotic Activity of DAB-15, a Novel Diazepinobenzimidazole Compound.

Antithrombotic activity of a new orally administered antiplatelet compound DAB-15 was compared to that of acetylsalicylic acid, ticlopidine, and clopidogrel in the experimental model of arterial thrombosis in rats caused by surface application of 50% ferric chloride (III) on the carotid artery. Compound DAB-15 exerted a dose-dependent antithrombotic effect and was superior to acetylsalicylic acid, ticlopidine and clopidogrel by 5, 7, and 4.9 times, respectively (by ED50). This necessitates studying of the action mechanism of this antiplatelet compound with consideration of its influence on different stages of the pathogenesis of platelet aggregation.

Effect of Compound Sbt-828, a New Indole Derivative Exhibiting Antiaggregant Activity, on the Prostacyclin-Thromboxane A2 Balance.

We investigated the effect of a new indole derivative Sbt-828 with antiaggregant properties on prostacyclin-generating activity of the vascular wall and thromboxane A2 level in platelets of intact rats. The substance under study did not affect prostacyclin production by the vascular wall and significantly reduced thromboxane A2 level, being superior to the reference drug acetylsalicylic acid by 1.6 times, as seen from reduced malonic dialdehyde level in the thrombin-induced rat platelets.

Effect of a New Antioxidant Enoxifol on Platelet Aggregation and Blood Rheological Properties in Rats with Experimental Diabetes Mellitus.

Effect of a new antioxidant enoxifol exhibiting antiplatelet activity in vitro and in vivo on hemostasis parameters was assessed in laboratory rats with experimental diabetes mellitus. Gliclazide, a hypoglycemic agent with antiplatelet properties, and pentoxifylline, a preparation improving blood rheology, were used as the reference drugs. Enoxifol produced a pronounced inhibitory effect on platelet aggregation in rats with experimental diabetes comparable to the effect of gliclazide and decreased blood viscosity thus demonstrating a significant effect comparable to that of pentoxifylline. In view of the fact that oxidative stress is a pathogenetic components of vascular complications in diabetes, it can be assumed that improvement of hemostasis parameters under the effect of enoxifol is determined by its antiplatelet and antioxidant activities.

[ANTIAGGREGANT ACTIVITY OF A NEW TRICYCLIC BENZIMIDAZOLE DERIVATIVE.]

The antiaggregant activity of a new benzimidazole derivative - 2,3,4,5-tetrahydro[1,3]diazepino[1,2-α]benzimidazole (DAB-15) has been investigated in vitro in comparison to reference drugs acetylsalicylic acid (ASA) and ticlid (ticlopidine) on the models of ASA, collagen, and epinephrine induced platelet aggregation in rabbits. It was established that DAB-15 exhibited dose-dependent antiaggregant activity. On the model of ASA-induced platelet aggregation, the effect of ADB-15 exceeded that of ASA and was slightly lower than that of ticlid. On the models of collagen, and epinephrine induced platelet aggregation, DAB-15 was reliably more active than the both reference drugs.

Antithrombotic Activity of a New Hypoglycemic Compound Limiglidole in Mouse Model of Cell Thrombosis.

Antithrombotic activity of hypoglycemic compound limiglidole that exhibits antiplatelet activity 2-fold exceeded activity of antiplatelet agent acetylsalicylic acid in the mouse model of systemic collagen-epinephrine thrombosis. Limiglidole signifi cantly reduced the relative and mean area of blood clots in the sections of mouse lungs.

Antithrombotic activity of a new benzimidazole derivative in the thrombosis model in mice.

Antithrombotic activity of a new benzimidazole derivative RU-891, characterized by antiaggregant activity, vs. reference drug acetylsalicylic acid was studied on the epinephrinecollagen thrombosis model in mice. Antithrombotic activity of RU-891 3-fold surpassed that of the reference drug. Histological studies showed that RU-891 significantly reduced the relative and mean areas of thrombi in sections of mouse lungs in comparison with the control.

Antiaggregant activity of a new benzimidazole derivative.

Antiaggregant activity of a new tricyclic benzimidazole derivative, RU-891 compound, was studied on the model of ADP-induced platelet aggregation in vitro and intravascular platelet aggregation in vivo. We evaluated the effect of this substance on blood coagulation potential. Antiaggregant agent acetylsalicylic acid was used as the reference drug. RU-891 produced a dose-dependent antiaggregant effect in vivo and in vitro that exceeded the effect of the reference drug. This compound did not modulate blood coagulation potential.

Antithrombogenic activity of antioxidant compounds.

Antithrombotic activities of enoxifol, a new antioxidant with antiaggregant activity demonstrated in vitro and in vivo, and antioxidant mexidol were compared on the rat model of arterial thrombosis induced by application of 50% ferric chloride. Acetylsalicylic acid (antiaggregant) served as the reference drug. All drugs exhibited dose-dependent antithrombotic activity. Enoxifol was more effective than mexidol, both drugs being more active than the reference drug (acetylsalicylic acid). Taking into account the pathogenesis of the thrombosis in this experimental model, we can hypothesize that the pronounced antithrombotic effect of enoxifol was due to its antiaggregant and antioxidant activities.