Inhibitors of aggregation

The discovery of inhibitors of fibrillogenesis has been hampered by the complexity of the folding pathway, the presence of mixed populations of aggregates, and the lack of sensitive markers of each oligomeric species.40 Screening assays based on thioflavin-S fluorescence or Congo-red absorbance have been used to identify inhibitors of aggregation of synthetic Af peptide. The reported compounds suffer from relatively low potency (effective at <10 pM) and "flat" SARs." 43... 

Silymarin derivatives (Taxifolin). Silymarin, the seed extract of Silybium marianum, has preventive effects against AD. Sato et al. [247] isolated (+)-taxifolin from silymarin as an inhibitor of aggregation of Ap42. 

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. 

Figure 3 Effect of seeding and inhibitors on aggregation reaction. The lag phase (curve c) is characteristic of reactions in which formation of nuclei for polymerization is an unfavorable process. Addition of preformed nuclei or seeds" (curve a) abolishes the lag phase. Inhibitors may affect the formation of nuclei and influence eitherthe lag phase, the extension of the nuclei changing the growth phase, or both (curve d). The inhibitor example (curve d) acts more strongly at nuclei formation than on the slope or plateau level of the growth phase.

Anagrelide -inhibitor of platelet aggregation which causes thrombocytopenia -cardiovascular effects (CHF, edema, palpitations) -anemia -nausea and vomiting -headache... 

SNAC is the most potent inhibitor of collagen-induced platelet aggregation in vitro compared to other S-nitrosothiols (SNAP, GSNO, CysNO and HomocysNo). Although it increased cGMP-levels in platelets [47], SNAC only partially inhibited thrombin-induced P-selectin expression on a platelet surface [79]. 

---