JTV-519 | Wikipedia audio article
Channel: wikipedia tts
Date: 2018-10-29

This is an audio version of the Wikipedia Article:
JTV-519

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SUMMARY
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JTV-519 (K201) is a 1,4-benzothiazepine derivative that interacts with many cellular targets. It has many structural similarities to diltiazem, a Ca2+ channel blocker used for treatment of hypertension, angina pectoris and some types of arrhythmias. JTV-519 acts in the sarcoplasmic reticulum (SR) of cardiac myocytes by binding to and stabilizing the ryanodine receptor (RyR2) in its closed state. It can be used in the treatment of cardiac arrhythmias, heart failure, catecholaminergic polymorphic ventricular tachycardia (CPVT) and store overload-induced Ca2+ release (SOICR). Currently, this drug has only been tested on animals and its side effects are still unknown. As research continues, some studies have also found a dose-dependent response; where there is no improvement seen in failing hearts at 0.3 μM and a decline in response at 1 μM.Treatment with JTV-519 involves stabilization of RyR2 in its closed state, decreasing its open probability during diastole and inhibiting a Ca2+ leak into the cell’s cytosol. By decreasing the intracellular Ca2+ leak, it is able to prevent Ca2+ sparks or increases in the resting membrane potential, which can lead to spontaneous depolarization (cardiac arrhythmias), and eventually heart failure, due to the unsynchronized contraction of the atrial and ventricular compartments of the heart. When Ca2+ sparks occur from the SR, the increase in intracellular Ca2+  contributes to the rising membrane potential which leads to the irregular heart beat associated to cardiac arrhythmias. It can also prevent SOICR in the same manner; preventing opening of the channel due to the increase of Ca2+ inside the SR levels beyond its threshold.