Antiaggregatorische und anticoagulante Eigenschaften von Oligoaminen, 9. Mitt. Zur Pharmakokinetik von N,N′,N″‐Tris‐4‐(3‐iod‐4‐methoxyphenyl)‐butyl‐1,3,5‐benzol‐triethanamin

Wolf

Wenzel

1995

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The pharmacokinetic behaviour of the 131-iodine-labelled title compound 3* and its metabolites in mice was investigated. A two phase, 1st order elimination profile was observed. The second phase is very slow leaving about 35% of radioactivity in the mice even 100 h after i.v. injection, because of high affinity to liver and spleen, caused by strong binding of oligoamines to phospholipids of liver and blood cell membranes. The blood-brain-barrier is not passed. No deep compartments were observed. The doses necessary for antithrombotic effects in vivo were calculated from the blood levels to be 20.5-39.7 mumol/kg for a time interval of 1-6 h after administration.

“…The activity in the tail is subtracted from the activity administered. The affinity of 32 to the different organs is determined according toequation (3). …”

Section: Organ Distribution Of Mdicuctivitymentioning

confidence: 99%

“…1) the concentration of 3 in whole blood and platelet-rich plasma (PRP) was calculated. This was performed with the higher dose only because of its relevance for antithrombotic effects.…”

mentioning

confidence: 99%

Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, XXX: Absorption, Organ Distribution, and Excretion of the Oligoamine (+)‐(S,S)‐1,4‐Bis‐[4‐(3‐iodo‐4‐methoxyphenyl)‐butylamino]‐butane‐2,3‐diol and its Metabolites

Wolf

Wenzel

1995

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Antiaggregatorische und anticoagulante Eigenschaften von Oligoaminen, 13. Mitt.: Verbesserung der Lagerfähigkeit von Vollblut und Erythrocytensuspensionen durch Oligoamine

Kaehler

Kuberka

1990

The impairment of the functions of red blood cells or their destruction during storage can be delayed or even inhibited by oligoamines especially RE 1492 (N,N',N''-Tris-(4-phenylbutyl)benzene-1,3,5-trimethanamine). When citrated whole blood (WB) is stored at 4 degrees C for 7 d half of the red blood cells (RBC) have lost their ability to form rouleaux. Addition of 100 mumols/L RE 1492 maintains 50% reaggregability up to day 28th of storage. When citrated WB is stored at 37 degrees C the reaggregability has declined to 40 percent after 10 h. With 100 mumols/L RE 1492 no reduction of this property is observed up to 48 h. These results are correlated with the maintainance of the discocyte form of RBC and a persistent filtrability of RBC suspensions through a 5 microns microporous membrane. With 100 mumols/L RE 1492 only one fifth of the haemolysis of untreated WB occurs. The efflux of potassium ions from RBC into the blood plasma during a 72 h storage is bisected by RE 1492. The binding of oxygen to RBC remains unchanged.

Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, XXIV: Interactions between Oligosydnone Imines and Albumine or Phospholipids

Piechocki

1994

Oligosydnone imines are strongly bound to albumin (alpha < 1%) in pure water. In saline, however, this effect is abolished (alpha approximately 80%). 4,4'-Propylene-bis-3-hexyl-sydnone-5-imine hydrochloride (1) moderately binds to phosphatidylcholine liposomes (PC, alpha approximately 34%). This is increased by phosphatidylethanolamine (PE). In PC/PE vesicles alpha is about 7%. The binding is further enhanced by the incorporation of negatively charged phospholipids (PL) like phosphatidylserine (PS). In PC/PE/PS liposomes complete binding of 1 can be achieved. This holds especially true if the composition of the liposomes is similar to the PL composition of platelet membranes. The results suggest that the antiplatelet activity of 1 is mediated by the bindings to negatively charged PL in the platelet membrane.