HIOC is a small-moleculeagent which acts as a selective TrkB receptoragonist (active at at least 100 nM; prominent activation at 500 nM).[1][2][3] It was derived from N-acetylserotonin (NAS).[2][3][4] Relative to NAS, HIOC possesses greater potency and a longer half-life (~30 min or less for NAS in rats, while HIOC is still detectable up to 24 hours after administration to mice; ~4 hour half-life for HIOC in mouse brain tissues).[2][3] It is described as producing long-lasting activation of the TrkB receptor and downstream signaling kinases associated with the receptor.[2] HIOC is systemically-active and is able to penetrate the blood-brain-barrier.[2] In animal studies, HIOC was found to robustly protect against glutamate-induced excitotoxicity, an action which was TrkB-dependent.[3]
^Longo, Frank M.; Massa, Stephen M. (2013). "Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease". Nature Reviews Drug Discovery. 12 (7): 507–525. doi:10.1038/nrd4024. ISSN1474-1776.
^ abcdeIuvone, P. Michael; Boatright, Jeffrey H.; Tosini, Gianluca; Ye, Keqiang (2014). "N-Acetylserotonin: Circadian Activation of the BDNF Receptor and Neuroprotection in the Retina and Brain". 801: 765–771. doi:10.1007/978-1-4614-3209-8_96. ISSN0065-2598. {{cite journal}}: Cite journal requires |journal= (help)
^ abcdShen, J.; Ghai, K.; Sompol, P.; Liu, X.; Cao, X.; Iuvone, P. M.; Ye, K. (2012). "N-acetyl serotonin derivatives as potent neuroprotectants for retinas". Proceedings of the National Academy of Sciences. 109 (9): 3540–3545. doi:10.1073/pnas.1119201109. ISSN0027-8424.
^Tosini, G.; Ye, K.; Iuvone, P. M. (2012). "N-Acetylserotonin: Neuroprotection, Neurogenesis, and the Sleepy Brain". The Neuroscientist. 18 (6): 645–653. doi:10.1177/1073858412446634. ISSN1073-8584.
