RESEARCH MONOGRAPH · KDC-MN-060

Org-26576

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

47/100

Organon's clinical-stage AMPA-PAM with mood-disorder data, mostly forgotten after acquisition

Org-26576 is another Organon ampakine that ran into the same fate as farampator. The molecule was a sulfonamide AMPA-PAM developed for cognitive impairment in depression and possibly schizophrenia, and it got through phase 1 and into phase 2 trials in major depressive disorder before the corporate machinations that swallowed the rest of Organon's CNS portfolio ended development. So we have a compound with real human exposure data that essentially stopped existing as a research target.

The published clinical data is thinner than for farampator but still substantial. The Nations group's work on cognitive measures in MDD patients and the safety pharmacology from the early-phase trials are the strongest pieces. The cognitive endpoint signal was modest, and notably the antidepressant efficacy signal that motivated the program wasnt strong enough to support continued development on its own.

The mechanism is the standard AMPA receptor positive allosteric modulation story, with pharmacokinetics that were apparently acceptable for chronic dosing. The Organon work suggested the molecule has some subunit selectivity but the details werent fully published.

What we like: real human data including controlled trials in a clinical population, safety profile that was reasonable through phase 2, and a depression-relevant cognitive signal thats worth comparing against the more famous ampakines.

What we dont like: limited published mechanistic detail (much of the receptor pharmacology was kept proprietary), the development halt means we never got the longer-term safety and efficacy readout, and the published clinical data is constrained enough that interpretation is difficult.

For research, Org-26576 is mostly of comparative interest. If you're doing AMPA-PAM work across multiple compounds it's worth having in the comparison set, particularly given the mood-disorder context of its clinical work. As a standalone research tool the literature is too thin to recommend it over better-characterized options.

Sourcing is poor. The molecule was never a commercial research reagent and supplier availability is genuinely limited. The few specialty vendors that produce it have variable characterization, and reference standards are difficult. HPLC and mass-spec verification are essential.

One of several orphaned AMPA-PAMs from the Organon era. Worth knowing about, hard to actually work with.

Evidence: 40
Mechanism: 60
Reliability: 55
Safety: 60
Sourcing: 35
Value: 40
Signal: 45
Staying power: 40

Plain-language summary Intrigue 40 / 100

Org-26576 is a sulfonamide AMPA potentiator developed at Organon. Phase 2 trials investigated it in major depressive disorder and ADHD. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Sulfonamide AMPA potentiator

An Organon/Merck ampakine that reached Phase 2 in major depressive disorder.

Abstract

Org-26576 is a sulfonamide-class AMPA receptor positive allosteric modulator developed by Organon (subsequently Schering-Plough, Merck) for cognitive enhancement in major depressive disorder and other indications. The compound advanced through Phase 2 trials with results consistent with the ampakine class profile (modest cognitive endpoint improvements, no adverse signal). The development program was discontinued under Merck. Pharmacokinetics: plasma half-life approximately 5 hours; oral bioavailability adequate. The compound is rarely available in research-chemical-grade markets.

Mechanism of action

AMPA receptor positive allosteric modulator (sulfonamide class).

Reported research dose ranges

Not in widespread research-chemical use.

References

Nations KR, et al. Examination of Org 26576, an AMPA receptor positive allosteric modulator, in a Phase 2 trial in major depressive disorder. J Psychopharmacol 2012.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, reported research dose ranges, sourcing and quality verification, reconstitution and handling, stack interaction considerations, and a curated reference list. Available as a research-use-only PDF download.

KDC-MN-060

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

Kodiac sells research compounds for investigative use only.

Org-26576

Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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