ABSTRACT
We have studied the effect of the new benzimidazole derivative RU-891, known to exhibit antiaggregant activity in vitro and in vivo, on the level of intracellular calcium ions in platelets of laboratory rabbits. Compound RU-891 was found to inhibit the thrombin-induced growth of intracellular calcium ion level in thrombocytes.This effect exceeded t he action o f reference d rugs and was not connected w ith the influence of RU-891 o n the potential-dependent c alci u m channels.
Subject(s)
Benzimidazoles/pharmacology , Blood Platelets/drug effects , Calcium/metabolism , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Animals , Blood Platelets/cytology , Blood Platelets/metabolism , Calcimycin/pharmacology , Calcium Channels/metabolism , Calcium Ionophores/pharmacology , Cells, Cultured , Dose-Response Relationship, Drug , Rabbits , Thrombin/antagonists & inhibitors , Thrombin/pharmacologyABSTRACT
Antithrombotic action of the novel benzimidazole derivative RU-891 exhibiting antiaggregant activity both in vitro and in vivo has been investigated in comparison to acetylsalicylic acid using the method of thrombosis induced by 50% ferrous chloride solution in rats. RU-891 compound showed dose-dependent antithrombotic activity exceeding that of the reference drug. Taking into account pathogenesis of this experimental thrombosis, it can be suggested that the antithrombotic action ofRU-891 is connected to its antiaggregant activity.
Subject(s)
Benzimidazoles/pharmacology , Blood Platelets/cytology , Fibrinolytic Agents/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Thrombosis/drug therapy , Animals , Animals, Outbred Strains , Aspirin/pharmacology , Blood Platelets/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Ferrous Compounds , Male , Rabbits , Rats , Thrombosis/chemically inducedABSTRACT
The effects of hypoglycemic drugs (gliclazide, glibenclamide) and new sugar-lowering drug diabenol on the coagulation chain of hemostasis and fibrinolytic system of blood have been studied in intact rats and in rats with experimental diabetes mellitus. Experiments revealed the ability of drugs to reduce thromboelastogram indices, which is probably related to the ability of hypoglycemic drugs to inhibit the platelet aggregation and prevent the subsequent activation of the coagulation chain of hemostasis. All drugs improve the thrombogenic potential (by decreasing the platelet activation) and increase the activity of the fibrinolytic system of blood. The activity of diabenol and gliclazide i s more pronounced as compared to that of glibenclamide.
Subject(s)
Fibrinolysis/drug effects , Hypoglycemic Agents/pharmacology , Platelet Aggregation/drug effects , Animals , Female , Hypoglycemic Agents/adverse effects , Male , Rats , ThrombelastographyABSTRACT
The hemorheological activity of a series of hypoglycemic drugs and the new antidiabetic agent RU-254 (9-diethylaminoethyl-2,3-dihydroimidazo[1, 2-a]benzimidazole dihydrochloride) was studied by comparative tests on rats with model diabetes. All the tested drugs reduce the number of ADP-activated platelet forms, inhibit platelet aggregation, and decrease the blood viscosity in both intact rats and the animals with streptosotocin-induced diabetes. RU-254 exhibited maximum activity with respect to a complex of hemorheological parameters. Glyclazide was less effective in this respect than RU-254, but exceeded the activity of both glybenclamide and glydifen.
Subject(s)
Blood Viscosity/drug effects , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/pharmacology , Platelet Aggregation/drug effects , Animals , Diabetes Mellitus, Experimental/blood , Drug Evaluation, Preclinical , Female , Male , RatsABSTRACT
We have compared the inhibitory effects of a series of hypoglycemic drugs, including glyclazide, glibenclamide, glucophage, rosiglitazone, diabenol (a new antidiabetic drug), and acetylsalicylic acid (reference antiaggregant preparation), on rabbit platelet aggregation in vitro induced by adding 5 mM ADP solution. All hypoglycemic drugs and acetylsalicylic acid inhibited platelet aggregation in a dose-depended manner. Diabenol, glyclazide and glibenclamide demonstrated the most pronounced activity in comparison to that of acetylsalycilic acid. A comparison of the published data on maximum drug concentrations in the blood plasma (Cmax) and the values of effective concentrations (EC25) of drugs determined in this study suggests that diabenol and glyclazide will produce direct antiaggregant effect under clinical administration conditions. At the same time, it is concluded that the antiaggregant effect of glibenclamide, glucophage and rosiglitazone is indirect and can only be pronounced at concentrations significantly exceeding the therapeutic level.
Subject(s)
Hypoglycemic Agents/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Animals , Aspirin/pharmacology , Dose-Response Relationship, Drug , RabbitsABSTRACT
The effect of the intravenous laser blood (ELB) treatment on the sensitivity of blood components with respect to drugs was studied in patients with nonspecific reactive hepatitis and chronic hepatitis. An ELB course reduced the functional activity of thrombocytes in the presence of fibrinogen and adrenaline hydrochloride (collagen inductors), which must be taken into account when these drugs are used as hemostatic agents.
