EGIS-12,233 gained my interest a while back, it looks like a novel 5-HT6 and 5-HT7 antagonist with seemingly no affinity at other receptors - it is demonstrated to increase dopamine release in cochlear tissue; thus improving hearing and reversing some forms of hearing loss.
http://www.ncbi.nlm.nih.gov/pubmed/18663573
http://www.ncbi.nlm.nih.gov/pubmed/18361484
http://en.wikipedia.org/wiki/EGIS-12,233
My interest is in it's general role as a 5-HT6/7 antagonist, given the known roles of these receptors, we could be looking at pro-cognitive effects as well being able to counter-act hypo-thermia associated with serotonin issues and serotonin syndrome - it also could prove valuable as an anti-depressant whilst being used in conjunction with an SSRI to help counter-act the side-effects of it.
http://www.ncbi.nlm.nih.gov/pubmed/18663573
http://www.ncbi.nlm.nih.gov/pubmed/18361484
http://en.wikipedia.org/wiki/EGIS-12,233
My interest is in it's general role as a 5-HT6/7 antagonist, given the known roles of these receptors, we could be looking at pro-cognitive effects as well being able to counter-act hypo-thermia associated with serotonin issues and serotonin syndrome - it also could prove valuable as an anti-depressant whilst being used in conjunction with an SSRI to help counter-act the side-effects of it.
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1375-80. Epub 2003 Jan 15.
No hypothermic response to serotonin in 5-HT7 receptor knockout mice.
Hedlund PB1, Danielson PE, Thomas EA, Slanina K, Carson MJ, Sutcliffe JG.
Author information
Abstract
With data from recently available selective antagonists for the 5-HT(7) receptor, it has been hypothesized that 5-hydroxytryptamine (5-HT)-induced hypothermia is mediated by the 5-HT(7) receptor, an effect previously attributed to other receptor subtypes. It has been established that the biologically active lipid oleamide allosterically interacts with the 5-HT(7) receptor to regulate its transmission. The most well characterized effects of oleamide administration are induction of sleep and hypothermia. Here, we demonstrate, by using mice lacking the 5-HT(7) receptor, that 5-HT-induced hypothermia is mediated by the 5-HT(7) receptor. Both 5-HT and 5-carboxamidotryptamine, a 5-HT(1) and 5-HT(7) receptor agonist, in physiological doses fail to induce hypothermia in 5-HT(7) knockout mice. In contrast, oleamide was equally effective in inducing hypothermia in mice lacking the 5-HT(7) receptors as in wild-type mice. When administered together, 5-HT and oleamide showed additive or greater than additive effects in reducing body temperature. Taken together, the results show that 5-HT-induced hypothermia is mediated by the 5-HT(7) receptor, and that oleamide may act through an independent mechanism as well as at an allosteric 5-HT(7) receptor site to regulate body temperature.
