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The enantiomers of the potent σ1 receptor antagonist (±)-1 were synthesized and evaluated for their affinity at σ1, σ2 receptors and dopamine transporter (DAT). Analogously to (±)-1, both the enantiomers showed very high affinity for the σ1 receptor and unprecedented selectivity over both the σ2 receptor and DAT. The lack of enantioselectivity between (+)-1 and (-)-1 indicated that the center of chirality in 2-position of the benzothiochromane nucleus doesn't play a crucial role in the interaction with any of the studied targets. Docking studies confirmed that the configuration of the enantiomers has only marginal effects on the molecular interactions with the σ1 receptor. In in vivo studies in a female rat model of binge eating, (±)-1 dose-dependently decreased the binge eating episode elicited by a history of intermittent food restriction and stress, confirming and strengthening the important role played by the σ1 receptor in bingeing-related eating disorders.
This article was published in the following journal.
Name: ACS chemical neuroscience
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An angiopoietin that is closely related to ANGIOPOIETIN-1. It binds to the TIE-2 RECEPTOR without receptor stimulation and antagonizes the effect of ANGIOPOIETIN-1. However its antagonistic effect may be limited to cell receptors that occur within the vasculature. Angiopoietin-2 may therefore play a role in down-regulation of BLOOD VESSEL branching and sprouting.
Cell surface receptors that bind to and internalize SECRETED PHOSPHOLIPASES A2. Although primarily acting as scavenger receptors, these proteins may also play a role in intracellular signaling. Soluble forms of phospholipase A2 receptors occur through the action of proteases and may a play a role in the inhibition of extracellular phospholipase activity.
A spectroscopic technique which uses the Mossbauer effect (inelastic scattering of gamma radiation resulting from interaction with heavy nuclei) to monitor the small variations in the interaction between an atomic nucleus and its environment. Such variations may be induced by changes in temperature, pressure, chemical state, molecular conformation, molecular interaction, or physical site. It is particularly useful for studies of structure-activity relationship in metalloproteins, mobility of heavy metals, and the state of whole tissue and cell membranes.
A family of receptors found on NK CELLS that have specificity for a variety of HLA ANTIGENS. KIR receptors contain up to three different extracellular immunoglobulin-like domains referred to as D0, D1, and D2 and play an important role in blocking NK cell activation against cells expressing the appropriate HLA antigens thus preventing cell lysis. Although they are often referred to as being inhibitory receptors, a subset of KIR receptors may also play an activating role in NK cells.
A disorder associated with three or more of the following: eating until feeling uncomfortably full; eating large amounts of food when not physically hungry; eating much more rapidly than normal; eating alone due to embarrassment; feeling of disgust, DEPRESSION, or guilt after overeating. Criteria includes occurrence on average, at least 2 days a week for 6 months. The binge eating is not associated with the regular use of inappropriate compensatory behavior (i.e. purging, excessive exercise, etc.) and does not co-occur exclusively with BULIMIA NERVOSA or ANOREXIA NERVOSA. (From DSM-IV, 1994)
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Adhd Anorexia Depression Dyslexia Mental Health Psychiatry Schizophrenia Stress Mental health, although not being as obvious as physical health, is very important, causing great unhappiness to those affected, causing add...