E-6837 is an orally active, 5-HT6 agonist developed in an attempt to create an anti-obesity medication. In cell lines expressing rat 5-HT6 receptors, it acted as a partial agonist (on presumed silent receptors), while it acted as a full agonist on human 5-HT6 receptors (which are constitutively active). Oral administration of E-6837 reduced food intake, but only transiently. In rats, twice daily administration of E-6837 over the course of 4 weeks resulted in a 15.7% reduction in body weight, compared to 11% reduction for sibutramine. This weight loss remained significant for E-6837 after a 43-day withdrawal period, whereas the weight difference was non-significant for sibutramine (i.e., sibutramine had a rebound effect while E-6837 did not), and this weight loss was found to be due to a loss of fat mass. The reduction in fat mass in E-6837 treated animals was associated with a 50% decrease in plasma leptin levels, and also reduced glucose and insulin levels in plasma after a glucose tolerance test. This indicates that weight loss from E-6837 is associated with improved insulin sensitivity, and thus, better glycemic control.[1][2][3]
One proposed mechanism of action is that E-6837 acts on neurons in the hypothalamus, which has shown significant levels of 5-HT6 receptor mRNA. The hypothalamus is one key structure involved in regulating food intake.[1]
^ abFisas, Angels (August 2006). "Chronic 5-HT6 receptor modulation by E-6837 induces hypophagia and sustained weight loss in diet-induced obese rats". British Journal of Pharmacology. 148 (7): 973–983. doi:10.1038/sj.bjp.0706807. PMC1751931. PMID 16783408.
^Kirkpatrick, Peter (1 August 2006). "Anti-obesity drugs: Fighting fat". Nature Reviews Drug Discovery. 5 (8): 634. doi:10.1038/nrd2123. S2CID 35924150.
^Garfield, A. S.; Heisler, L. K. (24 November 2008). "Pharmacological targeting of the serotonergic system for the treatment of obesity". The Journal of Physiology. 587 (1): 49–60. doi:10.1113/jphysiol.2008.164152. PMC2670022. PMID 19029184.
April 12, 2024
6837, orally, active, agonist, developed, attempt, create, anti, obesity, medication, cell, lines, expressing, receptors, acted, partial, agonist, presumed, silent, receptors, while, acted, full, agonist, human, receptors, which, constitutively, active, oral, . E 6837 is an orally active 5 HT6 agonist developed in an attempt to create an anti obesity medication In cell lines expressing rat 5 HT6 receptors it acted as a partial agonist on presumed silent receptors while it acted as a full agonist on human 5 HT6 receptors which are constitutively active Oral administration of E 6837 reduced food intake but only transiently In rats twice daily administration of E 6837 over the course of 4 weeks resulted in a 15 7 reduction in body weight compared to 11 reduction for sibutramine This weight loss remained significant for E 6837 after a 43 day withdrawal period whereas the weight difference was non significant for sibutramine i e sibutramine had a rebound effect while E 6837 did not and this weight loss was found to be due to a loss of fat mass The reduction in fat mass in E 6837 treated animals was associated with a 50 decrease in plasma leptin levels and also reduced glucose and insulin levels in plasma after a glucose tolerance test This indicates that weight loss from E 6837 is associated with improved insulin sensitivity and thus better glycemic control 1 2 3 E 6837 NamesPreferred IUPAC name 5 Chloro N 3 2 dimethylamino ethyl 1H indol 5 yl naphthalene 2 sulfonamideOther names E 6837IdentifiersCAS Number 528859 61 2 Y3D model JSmol Interactive imageChEMBL ChEMBL175835ChemSpider 5294027MeSH C500059PubChem CID 6918836UNII 4AXX8P95BU YInChI InChI 1S C22H22ClN3O2S c1 26 2 11 10 16 14 24 22 9 6 17 13 20 16 22 25 29 27 28 18 7 8 19 15 12 18 4 3 5 21 19 23 h3 9 12 14 24 25H 10 11H2 1 2H3Key OOIQBABUMXSCPC UHFFFAOYSA NSMILES CN C CCC1 CNC2 C1C C C C2 NS O O C3 CC4 C C C3 C CC C4 ClPropertiesChemical formula C22H22ClN3O2SMolar mass 427 95 g molExcept where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Infobox references One proposed mechanism of action is that E 6837 acts on neurons in the hypothalamus which has shown significant levels of 5 HT6 receptor mRNA The hypothalamus is one key structure involved in regulating food intake 1 See also editE 6801References edit a b Fisas Angels August 2006 Chronic 5 HT6 receptor modulation by E 6837 induces hypophagia and sustained weight loss in diet induced obese rats British Journal of Pharmacology 148 7 973 983 doi 10 1038 sj bjp 0706807 PMC 1751931 PMID 16783408 Kirkpatrick Peter 1 August 2006 Anti obesity drugs Fighting fat Nature Reviews Drug Discovery 5 8 634 doi 10 1038 nrd2123 S2CID 35924150 Garfield A S Heisler L K 24 November 2008 Pharmacological targeting of the serotonergic system for the treatment of obesity The Journal of Physiology 587 1 49 60 doi 10 1113 jphysiol 2008 164152 PMC 2670022 PMID 19029184 Retrieved from https en wikipedia org w index php title E 6837 amp oldid 1073999913, wikipedia, wiki, book, books, library,
