Itopride belongs to the same benzamide group as cisapride, a drug which was found to affect QT interval and possibly predispose those using it to cardiac arrhythmias. This resulted in cisapride being voluntarily removed from the U.S. market on July 14, 2000 after a warning letter was issued by the FDA which mentioned these effects. An obvious concern due to similarities between cisapride and itopride led to several preclinical studies being undertaken to evaluate the cardiac safety profile of itopride to see if it had a similar effect on QT interval in animals. These studies indicated that unlike cisapride, itopride was devoid of the potential to cause prolongation of the QT interval and posed no known risk of cardiac arrhythmias.
Later, in a study conducted with healthy adult volunteers, itopride was shown as unlikely to cause cardiac arrhythmias or ECG changes in part to the lack of significant interaction and metabolism via the cytochrome P450 enzyme pathway unlike cisapride and mosapride as it is metabolized by a different enzyme set. New molecular studies on guinea-pig ventricular myocytes also supported the cardiac safety profile of itopride as it did not affect certain potassium mechanisms that may have been affected by cisapride or mosapride. Moreover, itopride has no affinity for the 5-HT4 receptors unlike other benzamides such as cisapride and mosapride which are 5-HT4 agonists. The affinity of cisapride for 5-HT4 receptors in the heart has been implicated in the undesirable cardiac effects of cisapride itself.
The conclusion of this study revealed that itopride is devoid of any abnormal effect on QT interval. Therefore it may be possible that itopride could be considered as a better and certainly safer prokinetic agent than either cisapride or mosapride and itopride should also be considered a welcome treatment addition for symptomatic nonulcer dyspepsia and other gastric motility disorders.
... research into the role of PKC alpha in cardiac tissue has indicated that it has an important role in stimulating hypertrophy ... using mice, the transgenic overexpression of PKC alpha showed no effect on cardiac growth, and the inhibition of PKC alpha showed no effect on ... pointing in the direction that PKC alpha’s role in cardiac tissue has more impact as a regulator of contractility than of hypertrophy ...
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“You must train the children to their studies in a playful manner, and without any air of constraint, with the further object of discerning more readily the natural bent of their respective characters.”
—Plato (c. 427347 B.C.)