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JTV-519
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 Ca ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hydrochloride
In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternative name is muriate, derived from hydrochloric acid's ancient name: muriatic acid. Uses Converting amines into their hydrochlorides is a common way to improve their water solubility, which can be desirable for substances used in medications. The European Pharmacopoeia lists more than 200 hydrochlorides as active ingredients in medications. These hydrochlorides, compared to free bases, may more readily dissolve in the gastrointestinal tract and be absorbed into the bloodstream more quickly. Additionally, many hydrochlorides of amines have a longer shelf-life than their respective free bases. Amine hydrochlorides represent latent forms of a more reactive free base. In this regard, formation of an amine hydrochloride confers protection ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Catecholaminergic Polymorphic Ventricular Tachycardia
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited genetic disorder that predisposes those affected to potentially life-threatening abnormal heart rhythms or arrhythmias. The arrhythmias seen in CPVT typically occur during exercise or at times of emotional stress, and classically take the form of bidirectional ventricular tachycardia or ventricular fibrillation. Those affected may be asymptomatic, but they may also experience blackouts or even sudden cardiac death. CPVT is caused by genetic mutations affecting proteins that regulate the concentrations of calcium within cardiac muscle cells. The most commonly identified gene is RYR2, which encodes a protein included in an ion channel known as the ryanodine receptor; this channel releases calcium from a cell's internal calcium store, the sarcoplasmic reticulum, during every heartbeat. CPVT is often diagnosed from an ECG recorded during an exercise tolerance test, but it may also be diagnosed with a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Calcium Channel Blockers
Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as medications to decrease blood pressure in patients with hypertension. CCBs are particularly effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients. Calcium channel blockers are also frequently used to alter heart rate (especially from atrial fibrillation), to prevent peripheral and cerebral vasospasm, and to reduce chest pain caused by angina pectoris. N-type, L-type, and T-type voltage-dependent calcium channels are present in the zona glomerulosa of the human adrenal gland, and CCBs can directly influence the biosynthesis of aldosterone in adrenocortical cells, with consequent impact on the clinical treatment of hypertension with these agents. CCBs have been ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphorylation
In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be written in several ways that are nearly equivalent that describe the behaviors of various protonated states of ATP, ADP, and the phosphorylated product. As is clear from the equation, a phosphate group per se is not transferred, but a phosphoryl group (PO3-). Phosphoryl is an electrophile. This process and its inverse, dephosphorylation, are common in biology. Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License. Protein phosphorylation often activates (or deactivates) many enzymes. During respiration Phosphorylation is essential to the processes of both anaerobic and aerobic respiration, which involve the production of adenosine triphosphate (ATP), the "high-energy" exc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Kinase A
In cell biology, protein kinase A (PKA) is a family of serine-threonine kinases whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, including regulation of glycogen, sugar, and lipid metabolism. It should not be confused with 5'-AMP-activated protein kinase (AMP-activated protein kinase). History Protein kinase A, more precisely known as adenosine 3',5'-monophosphate (cyclic AMP)-dependent protein kinase, abbreviated to PKA, was discovered by chemists Edmond H. Fischer and Edwin G. Krebs in 1968. They won the Nobel Prize in Physiology or Medicine in 1992 for their work on phosphorylation and dephosphorylation and how it relates to PKA activity. PKA is one of the most widely researched Protein kinase, protein kinases, in part because of its uniqueness; out of 540 different protein kinase genes that make up the human kinome, only one other protein kinase, casein kinase ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Activation Energy
In the Arrhenius model of reaction rates, activation energy is the minimum amount of energy that must be available to reactants for a chemical reaction to occur. The activation energy (''E''a) of a reaction is measured in kilojoules per mole (kJ/mol) or kilocalories per mole (kcal/mol). Activation energy can be thought of as a magnitude of the potential barrier (sometimes called the energy barrier) separating minima of the potential energy surface pertaining to the initial and final thermodynamic state. For a chemical reaction to proceed at a reasonable rate, the temperature of the system should be high enough such that there exists an appreciable number of molecules with translational energy equal to or greater than the activation energy. The term "activation energy" was introduced in 1889 by the Swedish scientist Svante Arrhenius. Other uses Although less commonly used, activation energy also applies to nuclear reactions and various other physical phenomena. Temperature ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Spontaneous Depolarization , also known as spontaneism, the belief that social revolution can and should occur spontaneously without the aid or guidance of a vanguard party.
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Spontaneous may refer to: * Spontaneous abortion or miscarriage * Spontaneous bacterial peritonitis * Spontaneous combustion * Spontaneous declaration * Spontaneous emission * Spontaneous fission * Spontaneous generation * Spontaneous human combustion * Spontaneous Music Ensemble * Spontaneous order * Spontaneous process * Spontaneous remission * Spontaneous symmetry breaking * ''Spontaneous'' (album) by William Parker & the Little Huey Creative Music Orchestra * ''Spontaneous'' (film), an American romantic black comedy horror film See also * Revolutionary spontaneity Revolutionary socialism is a political philosophy, doctrine, and tradition within socialism that stresses the idea that a social revolution is necessary to bring about structural changes in society. More specifically, it is the view that revolu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Diastole
Diastole ( ) is the relaxed phase of the cardiac cycle when the chambers of the heart are refilling with blood. The contrasting phase is systole when the heart chambers are contracting. Atrial diastole is the relaxing of the atria, and ventricular diastole the relaxing of the ventricles. The term originates from the Greek word (''diastolē''), meaning "dilation", from (''diá'', "apart") + (''stéllein'', "to send"). Role in cardiac cycle A typical heart rate is 75 beats per minute (bpm), which means that the cardiac cycle that produces one heartbeat, lasts for less than one second. The cycle requires 0.3 sec in ventricular systole (contraction)—pumping blood to all body systems from the two ventricles; and 0.5 sec in diastole (dilation), re-filling the four chambers of the heart, for a total of 0.8 sec to complete the cycle. Early ventricular diastole During early ventricular diastole, pressure in the two ventricles begins to drop from the peak reached during systole ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Heart Failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF typically presents with shortness of breath, Fatigue (medical), excessive fatigue, and bilateral peripheral edema, leg swelling. The severity of the heart failure is mainly decided based on ejection fraction and also measured by the severity of symptoms. Other conditions that have symptoms similar to heart failure include obesity, kidney failure, liver disease, anemia, and thyroid disease. Common causes of heart failure include coronary artery disease, heart attack, hypertension, high blood pressure, atrial fibrillation, valvular heart disease, alcohol use disorder, excessive alcohol consumption, infection, and cardiomyopathy. These cause heart failure by altering the structure or the function of the heart or in some cases both. There are ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thiazepine
Thiazepines are substituted thiepins, with a nitrogen replacing a carbon in the seven-membered heterocyclic compound. Depending on the location of the nitrogen, one distinguishes 1,3-thiazepine and 1,4-thiazepine. Benzothiazepines have a single benzene attached to the ring, while dibenzothiazepines have two. Diltiazem, a benzothiazepine, is a calcium channel blocker intermediate in properties between verapamil and the dihydropyridines. It is used to treat variant angina (Prinzmetal's angina Variant angina, also known as Prinzmetal angina, vasospastic angina, angina inversa, coronary vessel spasm, or coronary artery vasospasm, is a syndrome typically consisting of angina (cardiac chest pain). Variant angina differs from stable angin ...), either naturally occurring or drug-induced and stable angina. References External links * {{heterocyclic-stub Thiazepines ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ryanodine Receptor
Ryanodine receptors (RyR) make up a class of high-conductance, intracellular calcium channels present in various forms, such as animal muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissues and participate in various signaling pathways involving calcium release from intracellular organelles. Structure Ryanodine receptors are multidomain homotetramers which regulate intracellular calcium ion release from the sarcoplasmic and endoplasmic reticula. They are the largest known ion channels, with weights exceeding 2 megadaltons, and their structural complexity enables a wide variety of allosteric regulation mechanisms. RyR1 cryo-EM structure revealed a large cytosolic assembly built on an extended Alpha solenoid, α-solenoid scaffold connecting key regulatory domains to the pore. The RyR1 pore architecture shares the general structure of the six-transmembrane ion channel superfamily. A unique domain inserted between the secon ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
