Non-steroidal and synthetic cardiotonic
This information is not intended for purposes of treatment without physician.
Description of the pharmacological group
Non-steroidal cardiotonic
Nonglycoside cardiotonic include the medicines of different mechanism of action and the chemical structures, which possess the ability to increase the force of the heart contractions. In contrast to cardiac glycosides they realize their positive inetropic action either by interaction with the receptor apparatus of cardiomyocytes, or via the blockade of the activity of the ferment of phosphodiesterase.
The starting gear, which causes the reduction of muscle cell, is the entering of the extracellular Ca2+ into its cytosol. This process is regulated by second Messenger - cAMP, which is formed from ATF with the aid of the ferment of adenylate cyclase connected with the membrane. The activity of adenylate cyclase can grow, for example, as a result of the stimulation of the β1- adrenoreceptors, located on the cellular membrane of cardiomyocytes. As a result the stimulation of β1- adrenoreceptors occurs the making more active of the specialized signal GS- proteins, which in turn activate ferment adenylate cyclase, which leads to an increase in the cell of concentration cAMP. The latter activates the ferment protein kinase, which the drive chain of the sequential biochemical processes, which lead to an increase in the entering of the ions Ca2+ inside the cardiomyocyte.
The different way, which makes it possible to increase the content cAMP, is the suppression of the activity of the ferment of phosphodiesterase, which stimulates the intracellular processes, which lead to the destruction cAMP. Suppression under the effect of of medicines of the activity of the ferment of phosphodiesterase entails an increase in the concentration in the cardiomyocytes cAMP, which in the final analysis leads to an increase in their reductibility.
Thus, to ensure strengthening the reductibility of heart muscle is possible by means of an increase in the content in the cardiomyocytes of second Messenger - cAMP, this it is possible to reach either by activating its synthesis, or by the suppression of the activity of the ferment, which participates in its destruction.
The medicines, which realize their cardiotonic action by increasing the content in the cardiomyocytes cAMP, can be classified as follows.
1. The medicines, which stimulate the activity of the ferment of adenylate cyclase:
a) of β1-adrenoceptor agonists - dopamine, dobutamine;
b) the stimulators of G2-glucogenic receptors - glucagon.
2. the means, which suppress the activity of the ferment of phosphodiesterase - amrinon, milrinon.
The search for new nonglycoside and nonadrenergic cardiotonic is directed toward obtaining of preparations with the large latitude of therapeutic action, the effectiveness with the different types of stagnant heart insufficiency, the presence of pharmacological properties, in particular vasodilator action additional useful with this pathology, which would improve not only the contracting ability of myocardium, but also it facilitated (“economizing”) its activities (see peripheral vasodilators).
Are at present obtained some synthetic nonglycoside and nonadrenergic cardiotonics (amrinon, milrinon, enoximon, piroximon and other). However, these preparations (with exception of amrinon and milrinon) did not find an an even wider practical use. At the same time possible to assume that the preparations of this group or close connections will enter into the arsenal cardiotonic of the means used.