Platelets antagonist

Junghans U, Seitz RJ, Ritzl A, Wittsack HJ, Fink GR, Freund HJ, Siebler M. Ischemic brain tissue salvaged from infarction by the GP Ilb/IIIa platelet antagonist tirofiban. Neurology 2002 58 474- 76. 

Becker RC. New thrombolytics, anticoagulants, and platelet antagonists the future of clinical practice. J Thromb Thrombolysis 1999 7 195-220. 

The methods described below outline three dynamic adhesion/aggregation assays used to assess the in vitro and/or ex vivo efficacy of platelet antagonists (1) a viscometric-flow cytometric assay to measure shear-induced platelet-platelet aggregation in the bulk phase, (2) a perfusion chamber coupled with a computerized videomicroscopy system to visualize in real time and quantify (a) the adhesion and subsequent aggregation of platelets flowing over an immobilized substrate (e.g. extracellular matrix protein) and (b) free-flowing monocytic cell adhesion to immobilized platelets. 

Incubate anticoagulated whole blood with platelet antagonist or vehicle (control) at 37 °C for 10 min. 

Expose the blood specimen, in the presence or absence of a platelet antagonist, to well-defined shear levels (typically 4000 sec-1 to induce significant platelet aggregation in the absence of a platelet antagonist) for prescribed periods of time (typically 30 to 60 sec). 

In some experiments, unbound platelet antagonist is removed by a brief washing step (4 min) prior to the perfusion of the cells of interest over the platelet layer. In others, the desirable concentration of the platelet antagonist is continuously maintained in the perfusion buffer during the entire course of the experiment. 

Abulencia JP, Tien N, McCarty OJT et al. (2001) Comparative antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist (XV454) and Abciximab (c7E3) in flow models of thrombosis. Arterioscler Thromb Vase Biol 21 149-156 McCarty OJ, Abulencia JP, Mousa SA, Konstantopoulos K (2004) Evaluation of platelet antagonists in in vitro flow models of thrombosis. Methods Mol Med 93 21-34... 

Activation of platelets is counteracted by biochemical processes which prevent agonist-induced responses. These are mainly mediated by the signaling molecules cAMP and cGMP, and all substances that induce an increase in one or both of diese are defined as platelet antagonists some of these are listed in table 9.5.1. 

Young s modulus for [CERAMICS - PffiCHANICAL PROPERTIES AND BEHAVIOR] (Vol 5) Platelet-activating factor QAE) antagonists... 

The synthetic utihty of the above transformations stems from the fact that many monoesters obtained as a result of hydrolysis may be converted to pharmaceutically important intermediates. For example, the optically active glycerol derivative (27) is a key intermediate in the production of P-blockers. Akyl derivative (25) may be converted into (5)-paraconic acid [4694-66-0] ((5)-5-oxo-3-tetrahydrofurancarboxyhc acid) that is a starting material for the synthesis of (3R)-A-factor. The unsaturated chiral cycHc monoacetate (31) is an optically active synthon for prostaglandins, and the monoester (29) is used for the synthesis of platelet activating factor (PAF) antagonists. 

Various 1.4-benzodiazepines with a five-membered heteroaromatic ring fused to the 1,2-bond, such as 17, where A represents a heteroaromatic ring, have been prepared by such methods and tested for activity on the central nervous system, as cholecystokinin antagonists and as antagonists of platelet activating factors.245... 

ACE inhibitors inhibit the degradation of bradykinin and potentiate the effects of bradykinin by about 50-100-fold. The prevention of bradykinin degradation by ACE inhibitors is particularly protective for the heart. Increased bradykinin levels prevent postischemic reperfusion arrhythmia, delays manifestations of cardiac ischemia, prevents platelet aggregation, and probably also reduces the degree of arteriosclerosis and the development of cardiac hypertrophy. The role of bradykinin and bradykinin-induced NO release for the improvement of cardiac functions by converting enzyme inhibitors has been demonstrated convincingly with use of a specific bradykinin receptor antagonist and inhibitors of NO-synthase. 

Intravenous and Oral Platelet Ub/fi3 Receptor Antagonists Potential Clinical Utilities... 

In some cases, substrate racemization can be achieved by an appropriate change of a functional group. A good example of this strategy is the synthesis of acid 10, which is the key intermediate for roxifiban - a potent selective antagonist of the platelet plycoprotein Ilb/IIa receptor (Scheme 5.8) [27, 28]. 

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