Ranolazine

Structural formula
1: 1 mixture of ( R ) -form (top) and ( S ) -form (bottom)
General
Non-proprietary name	Ranolazine
other names	( RS ) - N - (2,6-Dimethylphenyl) -2- [4- [2-hydroxy-3- (2-methoxyphenoxy) propyl] piperazin-1-yl] acetamide (±) - N - (2,6-Dimethylphenyl) -2- [4- [2-hydroxy-3- (2-methoxyphenoxy) propyl] piperazin-1-yl] acetamide DL - N - (2,6-Dimethylphenyl) -2- [4- [2-hydroxy-3- (2-methoxyphenoxy) propyl] piperazin-1-yl] acetamide
Molecular formula	C 24 H 33 N 3 O 4
External identifiers / databases
CAS number 95635-55-5 EC number 620-450-7 ECHA InfoCard 100.149.259 PubChem 56959 ChemSpider 51354 DrugBank DB00243 Wikidata Q907104
Drug information
ATC code	C01 EB18
Drug class	Coronary drugs
Mechanism of action	Sodium calcium channel inhibitors
properties
Molar mass	427.54 g · mol -1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS hazard labeling no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Ranolazine (trade name Ranexa ^® ; manufacturer Berlin-Chemie or Menarini ) is an antianginal drug from the group of piperazine derivatives that is used as an additional treatment for stable angina pectoris . Ranolazine works by reducing the sodium and calcium overload against the reduced blood flow to the heart muscle.

Clinical information

Approved areas of application

Ranolazine is approved for the relief of chest pain when the blood supply to the heart is insufficient (stable angina pectoris). It may only be used in addition to existing treatment in patients whose disease is not adequately controlled by other drugs such as beta blockers or calcium antagonists , or in patients who cannot tolerate these drugs.

unwanted effects

The following undesirable effects have been observed commonly during treatment with ranolazine: headache, tiredness, dizziness, constipation and feeling weak.

Interactions with other substances

Ranolazine is mainly metabolized via the cytochrome P450 3A4 and the cytochrome P450 2D6 . It also acts as an inhibitor on cytochrome P450 3A4 and P-glycoprotein . Numerous interactions are known about this metabolic pathway. Ranolazine can also increase the QT time and should not be used in conjunction with drugs that in turn extend the QT time. The pharmacist must therefore hand over a patient information card (PIK) with risk information every time ranolazine is dispensed.

Pharmacological properties

Mechanism of action

It is believed that ranolazine reduces the influx of sodium ions into the heart muscle cells . This in turn is said to reduce the activity of sodium-dependent calcium channels on the surface of the heart muscle cells. This reduces the number of calcium ions flowing in. Calcium ions are necessary for the heart muscle to contract . By reducing the influx of calcium, ranolazine contributes to the relaxation of the heart muscle during diastole, thereby improving the blood supply for the heart muscle and thus alleviating angina pectoris symptoms.

Chemical information

Ranolazine contains a stereocenter and is therefore a chiral substance. There are two enantiomers of ranolazine, the ( R ) form and the ( S ) form. The drug is a 1: 1 mixture of enantiomers ( racemate ). Both enantiomers are pharmacologically active.

criticism

The European Medicines Agency notes that Ranexa's effectiveness in improving symptoms in patients with stable angina is modest, but that it may be of benefit in patients who have not fully responded to other medicines. The prognosis of coronary artery disease is not significantly improved according to the randomized study MERLIN-TIMI 36 with 6500 patients with acute coronary syndrome. The arznei-telegramm regards the benefit-harm balance of ranolazine as negative based on the current state of knowledge. In a study published in The Lancet in January 2016, ranolazine did not improve the prognosis of recurrent coronary circulatory disorders or re-hospitalization in over 2,600 study participants after coronary angioplasty .

History

Ranolazine was first described in the accessible literature in 1987. It was initially developed by Syntex (now part of Roche ) and licensed out to CV Therapeutics in 1996.

In 2006 it was first approved as a drug in the USA. There ranolazine was marketed there by the company CV Therapeutics under the trademark Ranexa . The EU -approved was in mid-2008 under the trade name Latixa granted. A few weeks later, the trade name was also changed to Ranexa for the EU . In Switzerland ranolazine is approved since April of 2010.

Ranolazine is sold in the EU by the Italian company Menarini and in Germany by its subsidiary Berlin-Chemie .

literature

• S. Sossalla; Inhibition of the late influx of sodium (I _{Na, late} ) as a novel cardioprotective therapy option . In: Der Kardiologe , 2008, doi: 10.1007 / s12181-008-0070-4

Web links

• Entries in the NIH study registry

Individual evidence

1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
2. ↑ Ernst Mutschler, Gerd Geislinger, Heyo K. Kroemer, Sabine Menzel, Peter Ruth: Mutschler drug effects - pharmacology, clinical pharmacology, toxicology , 10th edition, Stuttgart, 2013, p. 538.
3. ↑ Summary of the product characteristics (PDF; 298 kB), as of July 2008, website of the European Medicines Agency, accessed on December 11, 2012.
4. ↑ Ranexa (ranolazine): Summary of the EPAR for the public (PDF; 44 kB) EMA; Retrieved August 8, 2010.
5. ↑ DA Morrow, BM Scirica, E Karwatowska-Prokopczuk, SA Murphy, A Budaj, S Varshavsky, AA Wolff, A Skene, CH McCabe, E Braunwald: Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial . PMID 17456819 .
6. ↑ Shelley Wood: MERLIN TIMI-36: Ranolazine fails for ACS, but safety record may bode well for angina labeling. theheart.org, March 7, 2007.
7. ↑ Ranolazine (Ranexa) in chronically stable angina pectoris . In: arznei-telegramm , 2009, 40, pp. 26-27.
8. ^ Giora Weisz, Philippe Généreux a. a .: Ranolazine in patients with incomplete revascularization after percutaneous coronary intervention (RIVER-PCI): a multicentre, randomized, double-blind, placebo-controlled trial. In: The Lancet , 387, 2016, p. 136, doi: 10.1016 / S0140-6736 (15) 00459-6 .
9. ↑ MC Allely, BJ Alps, AT. Kilpatrick: The effect of the novel anti-anginal compound RS 43285 on lactic acid, [K ⁺ ] and pH in a canine model of transient myocardial ischaemia . In: Biochem Soc Trans , 1987, 15, pp. 1057-1058.
10. ^ R. Jones: Ranolazine (Roche Bioscience) . In: IDrugs , 1999, 2, pp. 1353-1362. PMID 16113967 .

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !