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Biomedical subjects

F Markwardt

Publications and source records attributed to F Markwardt.

At least 163 records · Page 9Linked to original sources
PubMed1983

Characterization of alpha 2-adrenoceptors on blood platelets from various species using 3H-yohimbine.

Platelets from various mammalian species differ in the response to adrenaline mediated by activation of alpha 2-adrenoceptors. In contrast to platelets from rabbit, dog and man, adrenaline did not potentiate the ADP-induced aggregation of rat and guinea pig platelets. Binding assays with 3H-yohimbine, a selective alpha 2-adrenoceptor antagonist, showed that the radioligand was not bound specifically to rat and guinea pig platelets. The specific high affinity binding of 3H-yohimbine to intact human, dog and rabbit platelets was saturable and reversible. The Scatchard analyses of 3H-yohimbine binding showed that the number of binding sites and the affinity for the radioligand decreased in the order man greater than dog and dog greater than rabbit. The reduction in alpha-adrenoceptors on platelets seems to account for the diminished responsiveness to adrenaline.

Animals↗
PubMed1983

Influence of thrombin inhibitors on the thrombin-induced activation of human blood platelets.

The influence of thrombin inhibitors, which differ both in their chemical structure and type of inhibition, on the thrombin-platelet reaction was studied. The inhibitory effects of the competitive inhibitors tested on the thrombin-induced platelet reaction correlated well with their effects on the thrombin-catalyzed fibrinogen conversion and on the thrombin-catalyzed hydrolysis of synthetic substrates. Heparin and antithrombin III inhibited the thrombin-induced platelet reaction. However, heparin did not potentiate the inhibition by antithrombin III of the thrombin-platelet reaction.

Antithrombin III↗
PubMed1983

[Synthetic serine protease inhibitors. 29. Synthesis of alpha-arylsulphonylamino-beta-(4-amidinophenyl)ethyl-chloromethylketones and their inhibitory activity against trypsin, plasmin and thrombin].

The synthesis of alpha-arylsulphonylamino-beta-(4-amidinophenyl)ethyl-chloromethylketones, the structures of which correspond largely to those of the antiproteolytically very potent N alpha-arylsulphonylated 4-amidinophenylalaninamides, was realized starting from 4-cyanophenylalanine hydrochloride. After N alpha-arylsulphonylation this compound was converted via the acid chlorides by treatment with diazomethane into alpha-arylsulphonylamino-beta-(4-cyanophenyl)ethyl-diazomethylketones from which the corresponding chloromethylketones were afforded by treatment with concentrated hydrochloric acid. The conversion of the cyano function into the amidine function via the thiocarbamoyl and the thioimidic acid esters yielded the compounds named in the title. The substances produced no irreversible inhibition of the serine proteinases trypsin, plasmin and thrombin. Their competitive inhibitory effect was almost as potent as that of N alpha-arylsulphonylated 4-amidinophenylalanine ethylesters.

Amidines↗
PubMed1983

[Synthetic serine proteinase inhibitors. 30. Synthesis of alpha-benzoylamino-4-amidinocinnamic acid and alpha-(4-amidinobenzoylamino) cinnamic acid amides, and their inhibitory effect on trypsin-like enzymes].

To test their inhibitory activity against enzymes, the authors synthetized the compounds named in the title. The synthesis started from the corresponding azlactones 1 and 9. Subsequent aminolysis led to the alpha-benzoyl-aminocinnamic acid amides 2 and 10 which contain a cyano function. The acid amides were converted, in different ways, to the desired amidine salts 4, 7, 12 and 15. The amidines obtained showed but little inhibitory activity against the serine proteinases thrombin, trypsin and plasmin.

Amides↗
PubMed1983

[Visual evoked potentials in pattern motion].

Our intention was to obtain a visual evoked potential (VEP) consisting only of a movement-related component for the purpose of further investigations of movement detection. This was attempted by selection of appropriate stimulus conditions. Evoked by initial movement a VEP with five typical waves was observed at the human occipital scalp. The N2-wave with a peak latency of 180-200 ms was most prominent. Following results were yielded in the experiments carried out: 1. Adaptation to a pattern movement: The amplitude of N2 and P1 is significantly reduced (Fig. 4). 2. Relation between amplitude and velocity: The experimental data could be approximated by a power function with an exponent of m = 0.3 for N2 and lower m for later waves (Fig. 5). 3. Pattern variation (grating, checkerboard, zig-zag) had no influence on N2 but on P1 and possibly also on later waves (Fig. 6). These results suggest that the wave N2 is movement-related under our experimental conditions. A pattern-related component may additionally be assumed in wave P2. Components, evoked by further reasons, may be included in the waves following N2. Their specification demands supplementary experiments.

Evoked Potentials, Visual↗
PubMed1983

Chemical control of hyperfibrinolytic states by synthetic inhibitors of fibrinolytic enzymes.

The effects of two types of synthetic inhibitor of fibrinolytic enzymes (omega-aminocarboxylic acids, benzamidine derivatives) on intravascular fibrinolysis and fibrinogenolysis were studied in rats. Generalised primary fibrinogenolysis was produced by infusion of human plasminogen-streptokinase complex, secondary fibrinolysis was induced by infusion of the thrombin-like enzyme batroxobin. The inhibitors exerted different effects on the hyperfibrinolytic states. The omega-aminocarboxylic acids (PAMBA, AMCA) inhibited fibrinolysis more effective than fibrinogenolysis. In contrast, the benzamidines (APPA, NANP) were more potent inhibitors of fibrinogenolysis. Aprotinin examined for comparison behaved like the benzamidine derivatives.

4-Aminobenzoic Acid↗
PubMed1983

Comparative study on the antithrombotic effects of a synthetic thrombin inhibitor and of heparin in animal models.

The antithrombotic effects of the synthetic thrombin inhibitor 4-amidinophenylpyruvic acid and the naturally occurring thrombin inhibitor heparin were studied in a stasis-induced venous thrombosis model and an extracorporeal shunt model in rats. The incidence of venous thrombosis was reduced in a dose-dependent manner by both inhibitors. Thrombus size was reduced in the animals in which thrombi continued to form under treatment. The antithrombotic effect of the synthetic inhibitor was accompanied by considerable prolongation of the plasma thrombin time, whereas the effect of heparin on the thrombin time was less pronounced. The time until thrombotic occlusion of the extracorporeal arterio-venous shunt occurred was prolonged by both inhibitors in dependence upon the dose. The amount of thrombotic occluding material in the shunt was reduced and altered in composition. Synthetic thrombin inhibitors are potential antithrombotic agents whose effectivity corresponds to that of heparin.

Animals↗
PubMed1982

Pharmacological studies on the antithrombotic action of hirudin in experimental animals.

The pharmacodynamics and pharmacokinetics of hirudin were studied in dogs, rabbits and rats. Hirudin proved to be a well tolerated substance with low toxicity. After intravenous injection it was eliminated with a half time of 50 to 60 min. It was nearly completely excreted through the kidneys in biologically active form. The efficacy of hirudin in preventing venous thrombosis, vascular shunt occlusion and disseminated intravascular coagulation in rats was demonstrated.

Animals↗
PubMed1982

Dual effect of dihydroergotamine and dihydroergotoxin in isolated human femoral veins and arteries.

In human femoral vein strips, dihydroergotamine and dihydroergotoxin caused a slowly proceeding, long-lasting increase in tone. Dihydroergotamine had markedly higher affinity than noradrenaline, it possessed nearly the same intrinsic activity as noradrenaline. Dihydroergotoxin was less effective than dihydroergotamine. In isolated femoral artery strips, dihydroergotamine showed lower affinity and lower intrinsic activity in terms of noradrenaline. Dihydroergotoxin had negligible vasoconstrictor effects in arteries. In veins, dihydroergotoxin had a stronger alpha-adrenolytic effect than in arteries. In isolated arteries, dihydroergotoxin was equieffective to dihydroergotamine whose alpha-adrenoceptor blocking effect did not significantly differ in veins and arteries. Our results show that dihydroergotamine at very low concentrations exerted predominantly venoconstrictor effects and, therefore, it is more suited to increase the venous tone than dihydroergotoxin which at low concentrations showed alpha-adrenoceptor blocking activity.

Dihydroergotamine↗
PubMed1982

Influence of adrenergic neuron blocking agents on the adrenaline-induced platelet reactions.

Adrenaline causes aggregation of human blood platelets through stimulation of alpha-adrenoceptors resembling the alpha 2-type. Alpha-adrenoceptor blocking agents inhibit specifically the adrenaline-induced platelet reactions. The adrenaline-induced aggregation of human blood platelets was inhibited specifically by adrenergic neuron blocking agents such as guanoxan, guanclofine and guanethidine. Guanoxan (I50 = 0.6 mu mol/l) was about three orders of magnitude more effective than guanethidine, guanclofine occupied a median position. The compounds tested inhibited the ADP- and collagen-induced aggregation at relatively high concentrations. This is probably due to non-specific membrane effects. The known alpha-adrenolytic effect of guanoxan is believed to be mediated mainly by alpha 2-adrenoceptors.

Adrenergic beta-Antagonists↗
PubMed1982

Influence of benzamidine derivatives on thrombin-induced platelet reactions.

The influence of competitive synthetic thrombin inhibitors of the benzamidine type on the thrombin-platelet reaction was studied. The benzamidine derivatives tested inhibited thrombin-induced aggregation and 5-HT release in dependence upon their affinity for the enzyme. Accumulation of platelets in the lung of rats and the fall in platelet counts in the blood of rabbits induced by thrombin infusion were prevented by infusion of the inhibitors, as illustrated by example of 3-TAPAP. The thrombin-platelet reaction was inhibited at higher doses of inhibitor than those required for inhibition of coagulation. In this way, the inhibitors may exert a different influence on the various haemostatic steps.

Amidines↗
PubMed1982

[Synthetic inhibitors of serine proteinases. Part 26: Inhibition of trypsin, plasmin and thrombin by amides of N alpha-arylsulfonylated 2-amino-4-(4-amidino-phenyl) butyric acid and 2-amino-5-amidinophenyl valeric acids (author's transl)].

Among the derivatives of the N alpha-arylsulfonylated omega-amidinophenyl-alpha-aminoalkyl carboxylic acids, the primary amides of N alpha-arylsulfonylated 2-amino-4-(4-amidinophenyl) butyric acid proved to be compounds with strong antiplasmin and antitrypsin activity, they exert, however, only slight inhibitory effect on thrombin. So far, no benzamidine derivatives with strong inhibitory effects on plasmin but with weak antithrombin activity have been known. The secondary amides of the N alpha-arylsulfonylated 2-amino-4-(4-amidinophenyl)butyric acid possess slight inhibitory effects, the corresponding derivatives of 2-amino-5-amidinophenyl valeric acids, however, are potent inhibitors of thrombin.

Amidines↗
PubMed1982

[Pharmacokinetic studies with 3H-labelled synthetic antifibrinolytics].

In rabbits and rats pharmacokinetic studies on the anti-fibrinolytics 4-aminomethylbenzoic acid (PAMBA), trans-4-aminomethylcyclohexane-1-carboxylic acid (AMCA), and epsilon-aminocaproic acid (EACA) were carried out using the tritium labelled compounds. Following i. v. administration of PAMBA and EACA in rabbits a two-phasic plasma level and following AMCA a three-phasic plasma level was found within 7 h. The rate constants beta of 0.34 h-1, 0.44 h-1, and 1.08 h-1 for EACA, PAMBA, and AMCA, respectively, indicate a more rapid elimination of AMCA. Accordingly, the AUC-values for AMCA are considerably smaller than those for EACA and PAMBA after both i. v. and p. o. administration.

4-Aminobenzoic Acid↗