Sunifiram

Overview

Sunifiram (DM-235) is a synthetic non-peptide piperazine derivative marketed online as an 'ampakine-like' cognitive enhancer. Despite common branding, primary research shows it acts indirectly via the glycine-binding site of the NMDA receptor to potentiate AMPA-receptor-mediated transmission, not as a direct AMPA agonist. No human clinical trials or toxicology studies have been conducted, and sunifiram is not approved for any human or veterinary use worldwide. It is sold on the gray market without regulatory vetting.

Mechanism of Action

Sunifiram activates the glycine-binding site of the NMDA receptor in mouse hippocampal slices, triggering a PKCα/Src-family-kinase/CaMKII signaling cascade that increases phosphorylation of AMPA receptor subunits (GluR1 Ser-831), thereby potentiating AMPA-receptor-mediated synaptic transmission and long-term potentiation. This effect is blocked by the glycine-site antagonist 7-chloro-kynurenic acid but not by ifenprodil, confirming an indirect, NMDA-glycine-site-initiated mechanism rather than direct AMPA receptor agonism. Broad in-vitro receptor binding panels found no measurable affinity for major CNS receptors or channels, yet sunifiram increased acetylcholine release from rat cerebral cortex.

Research Summary

No human data exist. In olfactory-bulbectomized mice given oral sunifiram 0.01–1.0 mg/kg daily for 7–12 days, spatial reference memory (Y-maze) and short-term recognition memory (novel object recognition) improved, and impaired hippocampal CA1 long-term potentiation was restored via NMDAR-glycine-site-dependent CaMKII/PKC signaling (blocked by gavestinel). In mouse hippocampal slices, sunifiram (1–1000 nM, peaking at 10 nM with a bell-shaped dose-response) potentiated CA1 LTP via the glycine-site/PKCα/CaMKII pathway. In passive-avoidance models, sunifiram reversed amnesia in mice and rats at doses roughly four orders of magnitude lower than piracetam. No toxicology studies or human clinical trials have been conducted as of 2016.

Vendors selling Sunifiram

Scored vendors carrying Sunifiram, ranked by trust grade. Grades are computed from indexed Certificates of Analysis. Full $/mg pricing is on the comparison page.

Reported Side Effects

• No human toxicology or safety data exist
• No established toxicity threshold or adverse-effect profile
• Sold on gray market without regulatory approval or clinical vetting
• Not a controlled substance but unapproved for any use worldwide

Compare Sunifiram with Others

Research References

• Pharmacological Characterization of DM232 (Unifiram) and DM235 (Sunifiram), New Potent Cognition Enhancers. 2006.
• Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation in olfactory bulbectomized mice. 2013. PMID 23295391.
• Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine-binding site of N-methyl-D-aspartate receptor. 2013. PMID 23733502.
• PubChem Compound Summary for CID 4223812, Sunifiram.

Frequently asked questions

Has Sunifiram been independently lab-tested?

Disclosed Labs has collected 1 Certificate of Analysis (COA) for Sunifiram from 1 independent testing lab. 1 vendor has submitted material for testing. Products average 99.5% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/sunifiram/testing.

Where can researchers source Sunifiram?

1 vendor with Disclosed Labs trust grades currently list Sunifiram, including Kimera Chems. Compare live prices and lab-verified COAs at https://www.disclosedlabs.com/prices/sunifiram.

How does Sunifiram work?

Sunifiram activates the glycine-binding site of the NMDA receptor in mouse hippocampal slices, triggering a PKCα/Src-family-kinase/CaMKII signaling cascade that increases phosphorylation of AMPA receptor subunits (GluR1 Ser-831), thereby potentiating AMPA-receptor-mediated synaptic transmission and long-term potentiation. This effect is blocked by the glycine-site antagonist 7-chloro-kynurenic acid but not by ifenprodil, confirming an indirect, NMDA-glycine-site-initiated mechanism rather than direct AMPA receptor agonism. Broad in-vitro receptor binding panels found no measurable affinity for major CNS receptors or channels, yet sunifiram increased acetylcholine release from rat cerebral cortex.

What does the research say about Sunifiram?

No human data exist. In olfactory-bulbectomized mice given oral sunifiram 0.01–1.0 mg/kg daily for 7–12 days, spatial reference memory (Y-maze) and short-term recognition memory (novel object recognition) improved, and impaired hippocampal CA1 long-term potentiation was restored via NMDAR-glycine-site-dependent CaMKII/PKC signaling (blocked by gavestinel). In mouse hippocampal slices, sunifiram (1–1000 nM, peaking at 10 nM with a bell-shaped dose-response) potentiated CA1 LTP via the glycine-site/PKCα/CaMKII pathway. In passive-avoidance models, sunifiram reversed amnesia in mice and rats at doses roughly four orders of magnitude lower than piracetam. No toxicology studies or human clinical trials have been conducted as of 2016.