ORG-26576 - This looks interesting.
Stephen Clark
30 Sep 2017
Stumbled upon this while browsing. Looks interesting to me, sounds like it's got some potential. Thoughts?
ORG-26576 is an ampakine originally developed by Cortex Pharmaceuticals and then licensed to Organon International for development. In animal studies it has been shown to effectively potentiate AMPA receptor function, leading to increased BDNF release and enhanced neuronal differentiation and survival, as well as producing nootropic effects in standardised assays.[1][2][3][4][5][6] Development as an antidepressant has been halted due to a failed Phase II trial for major depressive disorder.[7]
https://en.wikipedia.org/wiki/ORG-26576
[1]. Jordan GR, et al. Regionally selective and dose-dependent effects of the ampakines Org 26576 and Org 24448 on local cerebral glucose utilisation
in the mouse as assessed by 14C-2-deoxyglucose autoradiography. Neuropharmacology. 2005 Aug;49(2):254-64.
[2]. Su XW, et al. Chronic treatment with AMPA receptor potentiator Org 26576 increases neuronal cell proliferation and survivalin adult rodent hippocampus. Psychopharmacology (Berl). 2009 Oct;206(2):215-22.
https://www.medchemexpress.com/Org-26576.html
**Forgive me for the terrible formatting. I'm not too familiar with formatting, as I haven't posted at length here yet.
Edited by Stephen Clark, 30 September 2017 - 06:39 AM.
noot_in_the_sky
12 Oct 2017
Uuuuh, we got ourself a new one 
Look at one of the abstracts:
Examination of Org 26576, an AMPA receptor positive allosteric modulator, in patients diagnosed with major depressive disorder: an exploratory, randomized, double-blind, placebo-controlled trial.Abstract
Org 26576 acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. The aim of this Phase 1b study (N=54) was to explore safety, tolerability, pharmacokinetics, and pharmacodynamics of Org 26576 in depressed patients. Part I (N=24) evaluated the maximum tolerated dose (MTD) and optimal titration schedule in a multiple rising dose paradigm (range 100 mg BID to 600 mg BID); Part II (N=30) utilized a parallel groups design (100 mg BID, 400 mg BID, placebo) to examine all endpoints over a 28-day dosing period. Based on the number of moderate intensity adverse events reported at the 600 mg BID dose level, the MTD established in Part I was 450 mg BID. Symptomatic improvement as measured by the Montgomery-Asberg Depression Rating Scale was numerically greater in the Org 26576 groups than in the placebo group in both study parts. In Part II, the 400 mg BID dose was associated with improvements in executive functioning and speed of processing cognitive tests. Org 26576 was also associated with growth hormone increases and cortisol decreases at the end of treatment but did not influence prolactin or brain-derived neurotrophic factor. The quantitative electroencephalogram index Antidepressant Treatment Response at Week 1 was able to significantly predict symptomatic response at endpoint in the active treatment group, as was early improvement in social acuity. Overall, Org 26576 demonstrated good tolerability and pharmacokinetic properties in depressed patients, and pharmacodynamic endpoints suggested that it may show promise in future well-controlled, adequately powered proof of concept trials.
