RESEARCH MONOGRAPH · KDC-MN-056

CX-614

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

Our opinion on this compound

55/100

High-affinity benzoxazine ampakine with the strongest preclinical neurotrophic data of the CX-series

CX-614 is where the Cortex ampakine program got genuinely interesting. The compound is structurally a benzoxazine like CX-546 but with substantially higher potency at the AMPA receptor positive allosteric site, and the in vivo pharmacology produced some of the strongest neurotrophic signals seen in the class. The Lauterborn group's work on BDNF and TrkB upregulation in hippocampus after CX-614 dosing is the headline result, and the magnitude of the effect is striking.

The mechanism story extends the CX-546 narrative. Sustained AMPA receptor potentiation upregulates immediate-early genes (Arc, Fos), drives BDNF transcription, and the downstream effects on synaptic plasticity and dendritic morphology have been documented in multiple groups. This is the closest the ampakine class has come to demonstrating a plausible neurorestorative mechanism, and the implications for neurodegeneration research are real.

The behavioral pharmacology supports the molecular story. Aged-rat cognitive paradigms respond, and the magnitude of effect tends to be larger than CX-516 or CX-546 at functionally similar AMPA potentiation. The pharmacokinetics are also better, the molecule has reasonable BBB penetration and sustained effect, which makes the chronic dosing schedules required for trophic effects practical.

What we like: the strongest neurotrophic data in the CX-series, mechanistically coherent pharmacology, and a real opening for AMPA-PAM-driven neuroprotection research. The behavioral signal is consistent with the molecular story in a way that's relatively rare for this class.

What we dont like: human data is essentially zero, the molecule never advanced clinically, and the higher potency comes with a narrower therapeutic window. AMPA over-activation pushes you toward excitotoxicity faster, and the safety pharmacology hasnt been fully worked out.

For research, CX-614 is the ampakine we'd use for trophic-signaling work. The BDNF and Arc upregulation is reproducible across labs and the effect size makes it useful as a positive control for AMPA-PAM-driven plasticity studies.

Sourcing is limited. Few suppliers carry it, characterization varies, and reference standards are difficult. HPLC and mass-spec verification are standard practice for serious work. Stability is fine in dry storage.

The most underappreciated ampakine in the lineup, honestly. The neurotrophic story deserves more attention.

Evidence: 35
Mechanism: 75
Reliability: 65
Safety: 50
Sourcing: 45
Value: 50
Signal: 65
Staying power: 55

Plain-language summary Intrigue 40 / 100

CX-614 is another benzoxazine ampakine in the Cortex series. Investigated in early clinical trials for cognitive impairment. 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.

Benzoxazine ampakine

A potent benzoxazine ampakine with research applications in BDNF upregulation and synaptic plasticity studies.

Abstract

CX-614 (2H,3H,6aH-pyrrolidino-[2,1-3',2']1,3-oxazino-[6',5'-5,4]benzo[e]1,4-dioxan-10-one; CAS 215923-55-0; molecular formula C16H17NO4; molecular weight 287.32) is a potent benzoxazine-class ampakine developed at Cortex Pharmaceuticals as part of the same program that produced CX-516 and CX-546. CX-614 shows substantially higher AMPA potentiation potency than CX-516 in cellular assays (approximately 100-fold greater per molecule). The compound has been used extensively as a research probe for BDNF upregulation studies; chronic ampakine treatment elevates hippocampal BDNF expression through transcriptional mechanisms downstream of AMPA potentiation, providing a pharmacological model for neurotrophin-mediated synaptic plasticity. CX-614 has not been advanced to human clinical trials. The compound is sold as a research chemical with limited availability.

Mechanism of action

Potent AMPA potentiator (benzoxazine class). Used as research probe for chronic AMPA stimulation effects on BDNF.

Reported research dose ranges

Sparse dosing data in the literature; principally a research probe.

References

Lauterborn JC, et al. Ampakines have similar acute effects on basal and stimulated BDNF mRNA expression. Brain Res 2003.
Mackowiak M, et al. Cortical and hippocampal BDNF response to ampakine treatment. Neuropharmacology 2002.

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-056

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.

CX-614

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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