Enoximone

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... 

Enoximone (113), an imidazdinone-containing molecule, is a cardiotonic molecule like imazodan above. Its mechanism of action is still not established but it is repotted to be a potent... 

CH4N2O 57-13-6) see Alfuzosin Allantoin Amobarbital Barbital Bromisoval Butalbital Carbasalate calcium Carbromal Cyclopentobarbital Dimethadione Dipyridamole Enoximone Ethotoin Heptabarb Metaxalone Methyclothiazide Orotic acid Paramethadione Pentobarbital Phenacemide Phenetuiide Phenobarbital Phenytoin Proquazone Secbutabarbital Secobarbital Sulfadimethoxine Thalidomide Trimethadione... 

CYP450 system Anagrelide enhanced the inhibition of platelet aggregation by aspirin and is an inhibitor of cyclic AMP PDE III (may exaggerate the properties of milrinone, enoximone, amrinone, olprinone, and cilostazol). 

Amrinone, milrinone, and enoximone differ from aminophylline in that they exhibit a certain degree of selectivity for peak III phosphodiesterase, which is found predominantly in myocardial and vascular tissues. These agents exert both positive inotropic and direct vasodilating actions (Figure 35.8). 

ENOXIMONE, MILRINONE ANAGRELIDE Risk of adverse effects... 

ENOXIMONE BRONCHODILATORS -THEOPHYLLINE Theophylline may si efficacy of enoximone... 

THEOPHYLLINE PHOSPHODIESTERASE INHIBITORS-ENOXIMONE Theophylline may i efficacy of enoximone Possibly competitive inhibition of phosphodiesterases Be aware watch for poor response to enoximone... 

The phosphodiesterase inhibitors, enoximone and milrinone have positive inotropic effect due to selective myocardial enzyme inhibition and may be used for short-term treatment of severe congestive cardiac failure. Evidence from longer term use indicates that these drugs reduce survival. 

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