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Non-glycosidic (nonsteroidal) and non-adrenergic synthetic cardiotonics

In connection with the prevalence of various forms of congestive heart failure, the severe outcomes of this pathology and the lack of existing cardiotonic drugs in recent years, the search for new synthetic cardiotonic drugs has begun. Cardiac glycosides, although highly effective, but their use is limited to a small breadth of therapeutic action, a significant number of side effects and contraindications.
The use of sympathomimetic (adrenergic) drugs (dobutamine, dopamine, etc.) is limited in connection with the need for their parenteral administration and the short-term effect. The search for new non-glycosidic and non-adrenergic cardiotonics is aimed at obtaining drugs with a wide breadth of therapeutic effect, effectiveness in various types of congestive heart failure, the presence of additional useful pathological properties of pharmacological properties, in particular vasodilating action, which would improve not only the contractility of the myocardium, but also "Economization") of his activity (see Peripheral vasodilators).
At present, some synthetic non-glycosidic and non-adrenergic cardiotonics have been obtained (amrinone, milrinone, enoximone, pyroximon, etc.). However, these drugs (with the exception of amrinone and milrinone) have not yet found wide practical application. However, it can be assumed that the drugs of this group or close compounds will be included in the arsenal of cardiotonic agents. Therefore, it is advisable to have basic information about these preparations. Amrinone is approved for use in our country.
According to available data, one of the main links in the biochemical mechanism of action of these drugs is the inhibition of phosphodiesterase (III), leading to the accumulation of cyclic AMP (cAMP) in the myocardial cells, activation of protein kinase, increase in the entry of Ca '+ ions into the cells and activation of the function of contractile proteins. It is possible that the positive inotropic effect of amrinone and its analogues is also due to the blockade of adenosine (A ~) receptors and a decrease in the negative inotropic effect of endogenous adenosine.

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The subgroup of cardiotonic drugs includes drugs: