montelukast and Thrombosis

Abdominal aortic aneurysm (AAA) is an asymptomatic dilatation of the vessel wall exceeding the normal vessel diameter by 50%, accompanied by intramural thrombus formation. Since the aneurysm can rupture, AAA is a life-threatening vascular disease, which may be amenable to surgical repair. At present, no pharmacological therapy for AAA is available. The 5-lipoxygenase (5-LOX) pathway of arachidonic acid metabolism leads to biosynthesis of leukotrienes (LTs), potent lipid mediators with pro-inflammatory biological actions. Among the LTs, cysteinyl-leukotrienes (cys-LT) are well-recognized signaling molecules in human asthma and allergic rhinitis. However, the effects of these molecules in cardiovascular diseases have only recently been explored. Drugs antagonizing the CysLT1 receptor, termed lukasts and typified by montelukast, are established therapeutics for clinical management of asthma. Lukasts are safe, well-tolerated drugs that can be administered during long time periods. Here we describe recent data indicating that montelukast may be used for prevention and treatment of AAA, thus representing a promising pharmacological tool for a deadly vascular disease with significant socio-economic impact.

Topics: Acetates; Aortic Aneurysm, Abdominal; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Blood Vessels; Cyclopropanes; Cysteine; Humans; Leukotriene Antagonists; Leukotrienes; Quinolines; Receptors, Leukotriene; Sulfides; Thrombosis

Increasing the affinity of diamidines for AT-rich regions of DNA has long been an important goal of medicinal chemists who wanted to improve the antiparasitic and antifungal properties of that class of derivatives. In recent years it was demonstrated that diamidines could interfere with many other biomolecular targets including ion channels as well as enzymes and modulate some RNA-protein, DNA-protein, and protein-protein interactions. It is therefore not surprising that diamidines now emerge as novel potential drug candidates for the treatment of various diseases, i.a. neurodegenerative disorders, acidosis-related pathological conditions, hypertension, thrombosis, type 2 diabetes, myotonic dystrophy, and cancers. A summary of the most striking results obtained to date in those domains is presented is this review.

Topics: Amidines; Animals; Diabetes Mellitus, Type 2; DNA; Enzymes; Humans; Hypertension; Ion Channels; Myotonic Dystrophy; Neoplasms; Neurodegenerative Diseases; Proteins; RNA; Thrombosis

The de novo development of myocarditis during left ventricular assist device support for dilated cardiomyopathy has not been previously described. We report a case of severe eosinophilic myocarditis associated with the use of leukotriene-receptor antagonist montelukast that developed during left ventricular assist device support accompanied by intra-device thrombus formation that was hemodynamically tolerated and subsequently discovered in the explanted heart. There may be no visible change in cardiac function as assessed by echocardiography, but the diagnosis should be entertained with the development of peripheral eosinophilia.

Topics: Acetates; Cardiomyopathy, Dilated; Cyclopropanes; Eosinophilia; Female; Heart Transplantation; Heart-Assist Devices; Humans; Leukotriene Antagonists; Middle Aged; Myocarditis; Quinolines; Sulfides; Thrombosis