CAMP-activating compounds

Theoretical explanations for the stimulatory activity of the methyl xanthines. These compounds inhibit phosphodiesterase reaulting in the prolonged activ of metabolic enzymes.Adenylate cyclase activity is modulated by the bindin free adenosine. The methyl xanthines are antagonists to adenosine but the bindings do not produce its modulating (inhibitory, attenuating) response. Therefore the end result is stimulatory in relation to cAMP activity. 

The data is based on the pECso values of the active compounds in the respective cAMP TRF screen. 

Phosphodiesterase Inhibitors. Because of the complexity of the biochemical processes involved in cardiac muscle contraction, investigators have looked at these pathways for other means of dmg intervention for CHF. One of the areas of investigation involves increased cycHc adenosine monophosphate [60-92-4] (cAMP) through inhibition of phosphodiesterase [9025-82-5] (PDE). This class of compounds includes amrinone, considered beneficial for CHF because of positive inotropic and vasodilator activity. The mechanism of inotropic action involves the inhibition of PDE, which in turn inhibits the intracellular hydrolysis of cAMP (130). In cascade fashion, cAMP-catalyzed phosphorylation of sarcolemmal calcium-channels follows, activating the calcium pump (131). A series of synthetic moieties including the bipyridines, amrinone and milrinone, piroximone and enoximone, [77671-31-9], C22H22N2O2S, all of which have been shown to improve cardiac contractiUty in short-term studies, were developed (132,133). These dmgs... 

Compound Y-590 (68) (CAS 70386-06-0) investigated in Japan, represents another potent antithrombotic pyridazinone derivative. In rat platelets, its IC50 value for ADP induced aggregation has been found to be 9 ng/ml. In ex vivo experiments (rats, rabbits oral administration) activity has been observed at doses of 0.1 and 0.01 mg/kg [258]. This activity has been attributed to the inhibition of cAMP degradation in platelets [259]. 

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