Sigma Receptors Ligands: New insights into the Cardioprotective Potential

Abstract

Cardiovascular diseases (CVDs) are primary reason of mortality and morbidity worldwide. Angina pectoris (AP), myocardial infarction (MI), silent myocardial ischemia and sudden cardiac death occur due to blockage in the coronary artery by atherosclerotic clot. Atherosclerotic clot is a systemic inflammatory process characterised by the accumulation and subsequent thickening of the wall by blood borne materials like low-density lipoproteins and macrophages/lymphocytes within the intima of arteries. These initial fatty streak lesions may also evolve into vulnerable plaques susceptible to rupture or erosion. Plaque rupture initiates both platelet adhesion and aggregation as well as the activation of the clotting cascade leading to so-called athero-thrombotic process and leads to coronary artery blockade. Coronary artery blockage interrupts the coronary blood supply leading to damage of myocardium. Multiple factors such as intra cellular (Ca2+, pH) and inter cellular (adhesion molecules) factors, inflammation, environmental toxins as well as metals and oxygen free radicals are involved in the pathogenesis of coronary artery diseases. Furthermore, certain sigma receptor ligands have been reported to show protective action against coronary artery diseases. Sigma receptor, a transmembrane protein, is expressed in many tissues including cardiovascular, liver and central nervous system. Sigma ligands significantly prevented the deviated biochemical parameters such as cardiac marker enzymes, lipid profile and antioxidant parameters to near normal status. Therefore, sigma receptor stimulation represents a new therapeutic strategy to prevent heart from ischemic and hypertrophic dysfunction in case of cardiovascular disorders. This review summarises the sigma receptors and cardioprotective potential of sigma receptor ligands. The article also provides a comprehensive account of structure, types and medical efficacy of cardioprotective sigma agonists.