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Biomedical subjects

F Markwardt

Publications and source records attributed to F Markwardt.

At least 181 records · Page 10Linked to original sources
PubMed1982

[Animal experiments on the pharmacokinetics of N alpha-tosyl-(3-amidinophenyl)alanine piperidide (TAPAP), a new thrombin inhibitor].

The pharmacokinetics of the synthetic thrombin inhibitor N alpha-tosyl-(3-amidinophenyl)alanine piperidide (TAPAP) was studied in rabbits using 3H-TAPAP. Concentrations in plasma, bile, urine and organs were determined by liquid scintillation counting. In plasma, moreover, the content of biologically active compound was measured by means of plasma thrombin-time determinations. After i.v. administration of doses of 1-10 mg TAPAP/kg a biphasic course of the plasma level resulted, the second phase of which has a half-time of about 5 h. This phase is considered to represent the elimination of a metabolite of TAPAP which no longer inhibits thrombin. The enteral absorption was incomplete after oral administration. Binding to plasma proteins amounted to about 50%. There was no preferential accumulation in organs or tissues. The bile contained relatively high levels of radioactivity in all routes of administration and doses studied. Elimination of TAPAP or of labelled metabolites is assumed to occur via this route.

Animals↗
PubMed1981

[Synthetic inhibitors of serine proteinases. Part 24: Inhibition of trypsin, plasmin and thrombin by cyclic amides of N alpha-arylsulfonylamidinophenyl-glycines (author's transl)].

Cyclic amides of n alpha-arylsulfonyl (3-amidinophenyl)glycine are potent inhibitors of the serine proteinase trypsin, plasmin and thrombin. The weak inhibitory activity of the corresponding 4-amidinophenylglycine derivatives cannot be explained in terms of the structure-activity relationships established for benzamidine derivatives. It might be caused by steric hindrance of enzyme-inhibitor interactions.

Amides↗
PubMed1981

[Synthetic inhibitors of serine proteinases. Part 25: Inhibition of trypsin, plasmin and thrombin by amides of N alpha-substituted amidinophenylalanines and 3-amidinophenyl-3-aminopropionic acids (author's transl)].

Amides of N alpha-substituted 3-amidinophenylalanine are potent inhibitors of the serine proteinases trypsin, plasmin and thrombin. They belong to the most potent inhibitors of these enzymes of the benzamidine type. In contrast, amides of 4-amidinophenylalanine possess weak inhibitory activity towards trypsin and plasmin. The cyclic amides of this group, however, are potent thrombin inhibitors. These derivatives are the first benzamidines with specific antithrombin activity. The isomeric compounds of 3-amidinophenyl-3-aminopropionic acids possess weak inhibitory effects on trypsin, plasmin and thrombin.

Amidines↗
PubMed1981

Studies on the fibrinolytic effect of ocrase.

The fibrino(geno)lytic activity of the non-specific proteolytic enzyme ocrase, a protease from Aspergillus ochraceus, was studied in rat plasma in vitro and in vivo. The proteolytic activity of ocrase was rapidly neutralized by plasmatic inhibitors. Ocrase concentrations which did not surpass the inhibitory capacity of rat plasma exerted predominantly fibrinolytic effects. Under these conditions, ocrase displayed a certain fibrin specificity causing thrombolysis.

Animals↗
PubMed1980

Anticoagulant and antithrombotic action of novel specific inhibitors of thrombin.

A series of new specific inhibitors of thrombin, cyclic amides of N alpha-arylsulfonyl-amidinophenylalanine, was studied for anticoagulant action in vitro and in vivo. The inhibitors showed strong anticoagulant effects in vitro. The time course of the anticoagulant effect of the inhibitors in rabbits and rats was monitored using plasma thrombin time determinations. In rats, the inhibitors prevented the formation of experimental venous thrombi and of thrombin-induced microthrombosis. The new derivatives of benzamidine presented may be useful as immediately acting anticoagulants.

Amidines↗
PubMed1980

Influence of hirudin on endotoxin-induced disseminated intravascular coagulation (DIC) in weaned pigs.

In weaned pigs endotoxin infusion caused pathological changes in the clotting system typical of consumption coagulopathy and DIC resulting in circulatory disturbances. Infusion of the specific thrombin inhibitor hirudin prevented the endotoxin-induced disorders such as haematological changes, microthrombosis in various organs and the increase in right ventricular pressure and in respiratory rate.

Animals↗
PubMed1980

Adrenaline-induced reactions of human platelets in hirudin plasma.

The anticoagulant used for blood collection may modify platelet aggregation. In platelet-rich citrated plasma, adrenaline induced biphasic aggregation accompanied by 14C-serotonin release, whereas in platelet-rich hirudin plasma it induced weak primary aggregation. In plasma from blood anticoagulated simultaneously with hirudin and citrate, adrenaline caused biphasic aggregation as it was observed in citrated plasma. Qualitative differences in platelet reaction in hirudin citrated plasma were found to be dependent on calcium ion concentration. Therefore, the deprivation of calcium ions by citrate is considered the cause of the adrenaline effect in citrated plasma.

Adenosine Diphosphate↗
PubMed1980

Synthetic inhibitors of serine proteinases. 22. Inhibition of acrosin by benzamidine derivatives.

A series of substituted benzamidines was tested for their inhibitory effects on boar acrosin. Substituents with electron-donating properties and small aliphatic residues increase the inhibitory activity of benzamidine, whereas aromatic residues have only a slight enhancing influence. Only substituents with a beta- or gamma-keto group increase the acrosin binding affinity by more than one order of magnitude. Comparison of the structure-activity relationships for the inhibition of acrosin and trypsin showed differences in the binding sites of both enzymes.

Acrosin↗
PubMed1980

Monitoring of microthrombosis in experimental animals by continuous recording of 125I-fibrin deposits and 51Cr-labelled platelets in the lungs.

A method for continuous monitoring of microthrombosis in the lungs is described. After injection of labelled fibrinogen and platelets the accumulation of these blood constituents was estimated during experimental disseminated intravascular coagulation (DIC) by radioactivity measurement on the body surface. By optimizing the measuring geometry of a single hole collimator for scintillation probes a high relative efficiency was attained and a defined area of the lung was viewed. This method allows recording of the trapping of fibrin and platelets in the lungs in experimental DIC and investigations on the pharmacological control of this condition.

Animals↗
PubMed1979

[Pharmacology of heparin].

After introductory notes on the history of heparin research the chemistry of this mucopolysaccharide is described. It is shown that the chemistry of heparin cannot be exactly described by one chemical formula because heparin represents a family of compounds with different chain-length. Molecular features responsible for the high structural specificity of anticoagulant activity are described. The present status of knowledge on the mechanism of the anticoagulant action of heparin is described in detail. It is shown that basic mechanism is the acceleration of the interaction of antithrombin III with the clotting factors IXa, Xa, XIa, XIIa, and thrombin which are known to be serine proteases. The effects of heparin of platelet function, lipid composition of blood, and on fibrinolysis reflect its complex influence on hemostasis. After a description of side effects and toxicity clinically relevant data on its pharmacocinetics are given.

Animals↗
PubMed1979

[Fundamentals of antithrombotic therapy].

The physiological and biochemical reactions leading to intravascular clot formation are reported on as far as their representation is required for an understanindg of the pathogenesis of thrombosis and its pharmacological control.

Antithrombin III↗
PubMed1979

[Pharmacology of oral anticoagulants].

The present view on the mechanism of vitamin K-dependent synthesis of the clotting factors II, VII, IX and X in the liver and its inhibition by 4-hydroxycoumarine and 1,3-indandione-type anticoagulants is given. The discovery of gamma-carboxyglutamyl residues in intact clotting factors and the role of this amino acid as the calcium-binding principle is pointed out. After general considerations on the pharmacokinetics of coumarine-type anticoagulants detailed information on the pharmacokinetics of phenprocoumon, almost exclusively used in the GDR, is presented. The importance of pharmacokinetic aspects for control of oral anticoagulation is emphasized. As a possible tool for evaluation of individual pharmacokinetic parameters during already ongoing medication the additional administration of a single dose of radioactively labelled anticoagulant is proposed. Toxic effects in case of overdosage, untoward reactions and interference with oral anticoagulants by comedication are described.

Administration, Oral↗