Davunetide
An eight-amino-acid fragment of a brain protein that reached phase 2 and 3 trials without proving a benefit
Davunetide, also called NAP or AL-108, is an eight-amino-acid peptide (NAPVSIPQ) taken from activity-dependent neuroprotective protein, which helps stabilise microtubules inside nerve cells. It was developed as an intranasal spray for memory disorders and schizophrenia. Its human trials were safe but did not meet their main goals, and later analyses have looked for effects in men and women separately. It is not approved anywhere.
What is it?
Activity-dependent neuroprotective protein (ADNP) is essential for brain development; mutations in its gene cause ADNP syndrome, a form of autism with intellectual disability. Davunetide is the eight-amino-acid stretch of ADNP, NAPVSIPQ, that laboratory studies identified as its smallest active fragment. It carries a short motif that lets it associate with microtubule end-binding proteins, and in cell studies it strengthened the interaction between tau and microtubules. That rationale led to trials in conditions involving tau, the microtubule protein that forms tangles in Alzheimer's disease and progressive supranuclear palsy.
The trials were consistent in one way: davunetide, given as a nasal spray, was well tolerated. Efficacy was another matter. In a 12-week randomised trial in people with amnestic mild cognitive impairment, the composite memory score did not differ from placebo, though two individual tests showed signals. In schizophrenia, the main cognitive battery did not change, while a measure of functional capacity favoured the drug. Neither was large enough to be decisive.
The decisive test was in progressive supranuclear palsy, a fatal tauopathy. In a phase 2/3 trial at 48 centres in six countries, 313 people took 30 mg twice daily or placebo for 52 weeks. The disease rating scale worsened by exactly the same median amount in both groups (11.8 points), daily-living scores were identical, and serious adverse events were equal (54 in each group, including 11 and 10 deaths). Nasal side effects were more common on the drug. Development for the condition stopped.
Since then, the laboratory that discovered ADNP has reanalysed the old trials by sex. It reports memory effects differing between men and women in the prodromal Alzheimer's trial; a 2026 reanalysis of the PSP data, using a shorter 10-item rating scale the FDA now recommends, reports a significant treatment effect favouring women; and a pharmacokinetic analysis of an intravenous trial in heart-bypass surgery reports different blood levels in men and women. These analyses were not the trials' pre-specified goals and come from the drug's originators; they generate hypotheses that new trials would need to test.
Davunetide has no approval and no legitimate supply outside clinical research. Anything sold under its names, NAP or AL-108, is an unregulated research chemical.
Mechanism of Action
Davunetide is a fragment of a protein that helps hold nerve cells' internal scaffolding together. The rationale is laboratory-based; no human trial has shown that it changes the course of disease.
Fragment of ADNP
NAPVSIPQ is the smallest active fragment of activity-dependent neuroprotective protein, a protein essential for brain formation whose loss causes ADNP syndrome.
Microtubule end-binding proteins
Its SxIP motif associates with the microtubule end-binding proteins EB1 and EB3; in cells, removing EB1 or EB3 abolished its protective effect, and it increased tau's interaction with microtubules.
Targeting tauopathies
Because tau detaches from microtubules and forms tangles in Alzheimer's disease and progressive supranuclear palsy, stabilising the tau-microtubule link was the reason for testing it in those conditions.
Intranasal delivery
It was given as a nasal spray to reach the brain; trial doses were 5 to 30 mg once or twice daily, and an intravenous form (AL-208) was tested around heart surgery.
Published Research
These are the human trials of davunetide, read from their PubMed abstracts.
Mild cognitive impairment: 12-week randomised trial
Intranasal AL-108 was safe and well tolerated, but the composite cognitive memory score did not differ from placebo; two individual memory and attention tests showed possible signals.
Cognition in schizophrenia
The MATRICS cognitive battery did not change significantly versus placebo, but functional capacity (UPSA) showed a significant treatment effect, with effect sizes of 0.74 and 0.48 at 5 and 30 mg.
Progressive supranuclear palsy: phase 2/3 trial, 313 patients
After a year, the disease rating scale (PSPRS) and daily-living scores changed identically on davunetide and placebo; serious adverse events were equal (54 in each group) and nasal side effects such as nosebleeds were more common on the drug.
Sex-specific reanalysis in prodromal Alzheimer's disease
Men showed dose-dependent gains on a delayed visual matching test, and women a high-dose gain in digit span over placebo; the authors call for sex-specific drug development.
PSP trial reanalysed by sex, with the 10-item scale
Using 52-week data and the FDA-recommended 10-item PSP rating scale, the originators report a significant treatment effect favouring women when time, sex and treatment interactions were modelled (P = 0.0005), with cognitive gains in women; a post hoc analysis of a trial that missed its primary endpoints.
Intravenous davunetide during heart-bypass surgery
An analysis of an intravenous trial (AL-208, NCT00404014) around coronary artery bypass grafting reports different drug levels in men and women, with possible dose-dependent accumulation in men; the authors relate this to sex-specific neuroprotection.
How it binds the microtubule machinery
NAP contains the SxIP motif that binds microtubule end-binding proteins; depleting EB1 or EB3 abolished its protection against zinc toxicity, and it increased EB1 comet density and tau-microtubule interaction in neuronal cells.
Dosing Data
Davunetide has no approved dose. Trials gave it as a nasal spray at 5 to 30 mg once or twice daily, for 12 to 52 weeks.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the trials above.
Contraindications & Cautions
Investigational; there is no label.
Legal Status
Davunetide is investigational.
Frequently Asked Questions
?What is davunetide?
An eight-amino-acid peptide from a brain protein called ADNP, tested as a nasal spray for memory problems, schizophrenia and progressive supranuclear palsy.
?Did davunetide work in trials?
It was safe, but its trials did not meet their main goals. Later reanalyses by sex reported some memory effects that still need confirming in new trials.
?Is davunetide available?
No. It is not approved anywhere and has no legitimate supply outside clinical research.
?Does davunetide work better in women?
Reanalyses by its originators report effects favouring women in the PSP trial, but they were not the trial's pre-specified goal; only a new trial designed to test it could confirm this.
?What happened in the PSP trial?
Among 313 patients over 52 weeks, the disease rating scale worsened by the same median 11.8 points on davunetide and placebo.
?Has davunetide been tested in ADNP syndrome?
Not in people, as far as the studies on this page show. ADNP syndrome, the autism-related disorder caused by mutations in the ADNP gene, is why the parent protein matters, but davunetide's human trials were in memory disorders, schizophrenia and PSP.
References
- [other] PubChem. Davunetide (CID 9832404): molecular formula C36H60N10O12, molecular weight 824.9. Read September 30, 2026.
- [pubmed] Morimoto BH, et al. "A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment." Dement Geriatr Cogn Disord, 2013;35(5-6):325-36. PMID: 23594991.
- [pubmed] Javitt DC, et al. "Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia." Schizophr Res, 2012;136(1-3):25-31. PMID: 22169248.
- [pubmed] Boxer AL, et al. "Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial." Lancet Neurol, 2014;13(7):676-85. PMID: 24873720.
- [pubmed] Gozes I, et al. "Davunetide sex-dependently boosts memory in prodromal Alzheimer's disease." Transl Psychiatry, 2024;14(1):412. PMID: 39358355.
- [pubmed] Shapira G, et al. "Opposite molecular sex correlations in tauopathy paralleled by motor and cognitive efficacy of davunetide in women." Mol Psychiatry, 2026. PMID: 42399413.
- [pubmed] Gozes I, et al. "Systemic davunetide provides sex-specific neuroprotection during Coronary Artery Bypass Grafting (CABG)." Transl Psychiatry, 2025;15(1):454. PMID: 41173865.
- [pubmed] Ivashko-Pachima Y, et al. "ADNP/NAP dramatically increase microtubule end-binding protein-Tau interaction: a novel avenue for protection against tauopathy." Mol Psychiatry, 2017;22(9):1335-1344. PMID: 28115743.
Sources & Citations
Every study on this page was read from its PubMed record; for approved products, indications, dosing and pharmacology come from the FDA label on DailyMed and approval details from Drugs@FDA, read September 30, 2026. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.