Piperazine, a Key Substructure for Antidepressants: Its Role in Developments and Structure-Activity Relationships.

Depression is the single largest contributor to global disability with a huge economic and social burden on the world. There are a number of antidepressant drugs on the market, but treatment-resistant depression and relapse of depression in a large number of patients have increased problems for clinicians. One peculiarity observed in most of the marketed antidepressants is the presence of a piperazine substructure. Although piperazine is also used in the optimization of other pharmacological agents, it is almost extensively used for the development of novel antidepressants. One common understanding is that this is due to its favorable CNS pharmacokinetic profile; however, in the case of antidepressants, piperazine plays a much bigger role and is involved in specific binding conformations of these agents. Therefore, in this review, a critical analysis of the significance of the piperazine moiety in the development of antidepressants has been performed. An overview of current developments in the designing and synthesis of piperazine-based antidepressants (2015 onwards) along with SAR studies is also provided. The various piperazine-based therapeutic agents in early- or late-phase human testing for depression are also discussed. The preclinical compounds discussed in this review will help researchers understand how piperazine actually influences the design and development of novel antidepressant compounds. The SAR studies discussed will provide crucial clues about the structural features and optimizations required to enhance the efficacy and potency of piperazine-based antidepressants.

Antidepressant potential of nitrogen-containing heterocyclic moieties: An updated review.

Depression is currently the fourth leading cause of disease or disability worldwide. Antidepressant is approved for the treatment of major depression (including paediatric depression), obsessive-compulsive disorder (in both adult and paediatric populations), bulimia nervosa, panic disorder and premenstrual dysphoric disorder. Antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. Many drugs produce an antidepressant effect, but restrictions on their use have caused controversy and off-label prescription a risk, despite claims of superior efficacy. Our current understanding of its pathogenesis is limited and existing treatments are inadequate, providing relief to only a subset of people suffering from depression. Reviews of literature suggest that heterocyclic moieties and their derivatives has proven success in treating depression.

Diagnosis of Supravalvular Aortic Stenosis by Transesophageal Echocardiography.

The role of transesophageal echocardiography (TEE) in diagnosis of disorders of the thoracic aorta is well established. In this report the TEE findings in an adult patient with supravalvular aortic stenosis are presented. This showed narrowing of the ascending aorta just above the sinuses, due to fibromuscular thickening, causing an hour-glass shaped deformity. The excellent image quality obtained by TEE is far superior to transthoracic echocardiography. Coronary artery ostial obstruction a known association of supravalvular aortic stenosis can be caused by different mechanisms including adherence of the aortic valve leaflet to the ridge of obstructive muscle or premature atherosclerosis. TEE can define the mechanism of coronary artery ostial obstruction associated with supravalvular aortic stenosis.