Platelets aggregation

In blood platelets approximately 60% of the ADP + ATP is contained in granules together with serotonin (5-hydroxytryptamine). These adenine nucleotides are relatively inert metabolically, as incubation of platelets with radioactive precursors does not lead to their labeling, whereas non-particulate nucleotides readily become highly labeled (see references 28, 29). 

The intra-platelet levels of cAMP can be stabilized by prostacyclin or its analogues (e.g., iloprost) or by dipyridamole. The former activates adenyl cyclase via a G-protein-coupled receptor the latter inhibits a phosphodiesterase that breaks down cAMP. 

The integrin (CPIIB/IIIA)-antago-nists prevent cross-Unking of platelets. Their action is independent of the ag-Liillmann, Color Atlas of Pharmacology 

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Prostacyclin I2 (PGI2) inhibits platelet aggregation and relaxes coronary arteries Like PGE2 and TXA2 it is formed from arachidomc acid via PGH2... 

Methylpyrazole has been investigated as a possible treatment for alcoholism. The stmcture—activity relationship (SAR) associated with a series of pyrazoles has been examined ia a 1992 study (51). These compounds were designed as nonprostanoid prostacyclin mimetics to inhibit human platelet aggregation. In this study, 3,4,5-triphenylpyrazole was linked to a number of alkanoic acids, esters, and amides. From the many compounds synthesized, triphenyl-IJT-pyrazole-l-nonanoic acid (80) was found to be the most efficacious candidate (IC g = 0.4 //M). 

Dismption of the endothehal surface of blood vessels expose coUagen fibers and connective tissue. These provide surfaces that promote platelet adherence, platelet release reaction, and subsequent platelet aggregation. Substances Hberated from the platelets stimulate further platelet aggregation, eg, adenosine diphosphate maintain vasoconstriction, eg, serotonin and participate in blood coagulation, eg, platelet Factors III and IV. In addition, the release reaction modifies platelet membranes in a manner that renders phosphoHpid available for coagulation. The thrombin [9002-04-4] elaborated by the coagulation mechanism is a potent agent in the induction of the platelet release reaction. 

Recently, Picciola et al. (81FES1037) prepared some 2iT-indazole derivatives containing a phenylalkanoic acid residue with potential antiinflammatory activity (693). M.G. 18755 (R = CHMeC02H, R = R = R = H) and its lysine salt, M.G. 18334, showed greater activity than ibuprofen, and the homologous butyric acid derivative M.G. 18860 showed good activity as a platelet aggregation inhibitor. 

Forskolin (5-[acetyloxy]-3-ethenyldodecahydro-6,10,10b-trihydroxy-3,4a,7,7,10a-penta-methyl-[3R- 3a-4aP, SP, 6P, 6aa,10a, lOaP, 10ba -lFf-naphtho[2,l-b]pyran-l-one) [66575-29-9] M 410.5, m 229-232°, 228-233°. Recrystd from CfiH6-pet ether. It is antihypertensive, positive ionotropic, platelet aggregation inhibitory and adenylate cyclase activating properties [Chem AbstrS9 1978 244150, de Souza et al. Med Res Rev 3 201 1983]. 

Thromboxane A2 is a potent platelet aggregating agent and vasodilator which undergoes rapid hydrolysis under physiological conditions (ti/2 32 sec. at pH 7 and 37°C). The synthesis of stable analogs was of interest for biological studies of this potent but evanescent prostanoid. 

Platelet activating factor (PAF) was first identified by its ability (at low levels) to cause platelet aggregation and dilation of blood vessels, but it is now known to be a potent mediator in inflammation, allergic responses, and shock. PAF effects are observed at tissue concentrations as low as 10 M. PAF causes a dramatic inflammation of air passages and induces asthma-like symptoms in laboratory animals. Toxic-shock syndrome occurs when fragments of destroyed bacteria act as toxins and induce the synthesis of PAF. This results in a drop in blood pressure and a reduced... 

It was discovered that 3-iiitro-2-piperidiiio-, 3-iiitro-7-piperidiiio-, and 7-A -diethaiiolamiiio-3-iiitro-l, 8-iiaphthyridiii-2(lH)-oiies and 2-diethanol-amino-7-piperidino-3-nitro-l,8-naphthyridine showed remarkable aetivity to inhibit human platelet aggregation in vitro indueed by araehidonie aeid, eollagen, and ADR Tliis aetivity was eomparable to papaverine, dipyridamole, and ibuprofen (94EJMC735). 

Itazigrel (137) is an antithrombotic compound because of its inhibition of platelet aggregation induced by collagen. It is synthe.sizcd froin l-bromo-l-(4-methoxy)benzoyl-4-methoxytol-uene (135) by reaction in the usual way with triflucffothioacetamide (136) to give itazigrel 471. 

Therapeutic Function Blood platelet aggregation inhibitor... 

Therapeutic Function Vasodilator and platelet aggregation inhibitor Chemical Name Papaverine adenosine 5-monophosphate Common Name Papaverine adenylate... 

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