PE-22-28 vs Rapastinel
Written by Aaron CuhaReviewed Sep 2026
The short answer
Two fast acting antidepressant peptides. One is experimental, and the other went all the way. Rapastinel lowered depression scores within hours in a 116 person trial. Then it failed three large final stage trials in about 1,500 people. Its edge over the dummy on the depression scale was 0.3, 0.1 and 1.0 points.
- PE-22-28 people
- 0
- PE-22-28 nulls
- 0
- Rapastinel people
- 2,614
- Rapastinel nulls
- 1
Dose
No human dose established
No published study on this page has given this compound to people and reported a result.
2 animal studies, no human study
Dose
No human dose established
Amounts that were given in studies sit in Human evidence on this page. None of them is a personal dose.
5 completed trials, 2,614 people given it
First-hand reports are counted on each profile and never added together. This page sets two published records side by side. It does not pick a winner.
Column A
PE-22-28PE-22-28 (spadin analogue)
An experimental peptide studied in mice for fast antidepressant effects and new brain cell growth. It blocks a potassium channel in the brain.
Column B
RapastinelRapastinel (GLYX-13), intravenous NMDA receptor glycine site partial agonist tetrapeptide
A drip given for depression. In a 116 person study, it lowered depression scores within hours. Then it failed three large final-stage trials in about 1,500 people. People on the dummy drip did just as well. The gaps between groups were a point or less on the depression score. Allergan stopped the programme in July 2019.
Side by side, on the facts we can check
| What we compare | PE-22-28 | Rapastinel |
|---|---|---|
| Category | Nootropic & CNS | Nootropic & CNS |
| FDA status | Not FDA-approved; experimental | Not FDA approved. Its final-stage studies in major depression missed their main goals (results posted on ClinicalTrials.gov 2019 to 2020). The company stopped them in July 2019. No further work on it. |
| Half-life | Short | Not reported |
| Molecular weight | ~800 Da | Not reported |
| How it works | It blocks TREK-1, a potassium channel tied to mood. In animals, that gave fast antidepressant-like effects. | In people, here is what is known. One drip of 5 or 10 mg/kg eased depression for about a week in a 116 person study. Weekly 450 mg doses did no better than a dummy in three large trials. In 107 healthy people, doses of 900 and 1,800 mg did not hurt driving in a simulator, while ketamine at 0.5 mg/kg did. Nobody has shown that rapastinel changes NMDA signals in a human brain. In animals and in a dish, rapastinel sticks to the NMDA receptor near the spot where glycine, a helper molecule, binds. At low amounts it boosts the receptor's signal. At high amounts it dampens it. That is the proposed reason only the middle doses worked in the early human study. Rodents showed the same pattern. In rodents, one dose quickly raised proteins at nerve connections and gave a long lasting antidepressant-like effect. That looks like ketamine, but without ketamine's way of plugging the receptor. In a 2022 rodent study it also sped recovery from morphine withdrawal and cut relapse to drug seeking. |
| Studies in people | 0 | 7 |
| Evidence | Animal or lab only: 2 animal studies, no human study | Strong: 5 completed trials, 2,614 people given it |
| Legal status, US | Not approved; research use only | Investigational, not approved |
Frequently asked questions
What is the difference between PE-22-28 and Rapastinel?
PE-22-28: An experimental peptide studied in mice for fast antidepressant effects and new brain cell growth. It blocks a potassium channel in the brain. Rapastinel: A drip given for depression. In a 116 person study, it lowered depression scores within hours. Then it failed three large final-stage trials in about 1,500 people. People on the dummy drip did just as well. The gaps between groups were a point or less on the depression score. Allergan stopped the programme in July 2019.
Which has stronger research evidence, PE-22-28 or Rapastinel?
Each compound gets a band worked out from facts we counted, with the math shown. PE-22-28 is Animal or lab only (2 animal studies, no human study). Rapastinel is Strong (5 completed trials, 2,614 people given it). That counts how much has been done in people. It does not rate whether either one works, and neither one is called the winner.
Are PE-22-28 and Rapastinel FDA-approved?
PE-22-28: Not FDA-approved; experimental. Rapastinel: Not FDA approved. Its final-stage studies in major depression missed their main goals (results posted on ClinicalTrials.gov 2019 to 2020). The company stopped them in July 2019. No further work on it..
Reviewed Sep 2026. This page puts two published records side by side. It is for learning, and it is not medical advice. When this site shows a dose, it is the dose a trial or a clinic actually used, or what people say they did, with the source attached. None of it tells you what to take.