E-6837
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| E-6837 | |
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5-chloro-N-(3-(2-(dimethylamino)ethyl)-1H-indol-5-yl)naphthalene-2-sulfonamide |
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| Properties | |
| Molecular formula | C22H22ClN3O2S |
| Molar mass | 427.95 g/mol |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) | |
| Infobox references | |
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]
See also [edit]
References [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. Retrieved 24 December 2011.
- ^ Kirkpatrick, Peter (1 August 2006). "Anti-obesity drugs: Fighting fat". Nature Reviews Drug Discovery 5 (8): 634–634. doi:10.1038/nrd2123.
- ^ 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.
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