PE-22-28 alternatives.
10 compounds compared to PE-22-28, ranked by published evidence tier and regulatory status, not by what's marketed hardest.
PE-22-28 is a seven-residue fragment of spadin, developed to block the TREK-1 potassium channel and studied as a fast-acting antidepressant candidate in rodents. Anyone searching for an alternative has usually hit the wall in its file: it is a preclinical research compound with no human data, no approval, and no approved medical use. There is no peptide in this mechanism class with human evidence behind it, so a like-for-like substitute does not exist. What the list below offers is other neuropeptides sharing a category, most of them equally untested in humans. For an actual treatment decision the relevant alternatives are approved medicines, which is a conversation for a clinician.
PE-22-28 is a synthetic seven-residue peptide corresponding to residues 22 to 28 of spadin, itself a fragment derived from the sortilin propeptide (also called neurotensin receptor-3).
- 01OxytocinS tierFDA-approvedPitocin
Acts through the central neuromodulation pathway, like PE-22-28. FDA-approved.
- 02SelankD tierResearch / preclinical
Acts through the central neuromodulation pathway, like PE-22-28. Research / preclinical.
- 03SemaxD tierResearch / preclinical
Acts through the central neuromodulation pathway, like PE-22-28. Research / preclinical.
- 04N-Acetyl Semax AmidateF tierResearch / preclinical
Acts through the central neuromodulation pathway, like PE-22-28. Research / preclinical.
- 05DSIPF tierResearch / preclinicaldelta sleep-inducing peptide
Acts through the central neuromodulation pathway, like PE-22-28. Research / preclinical.
- 06CerebrolysinC tierResearch / preclinicalporcine brain peptide preparation
Same category: cognition & mood. Research / preclinical.
- 07CortexinD tierResearch / preclinicalcattle brain polypeptides
Same category: cognition & mood. Research / preclinical.
- 08P21F tierResearch / preclinicalP021 · CNTF-derived peptide mimetic
Same category: cognition & mood. Research / preclinical.
- 09DihexaF tierResearch / preclinical
Same category: cognition & mood. Research / preclinical.
- 10PinealonF tierResearch / preclinical
Same category: cognition & mood. Research / preclinical.
An “alternative” here means a compound that shares PE-22-28's mechanism pathway or sits in the same category, not a marketing substitute. Each is ordered by PepCue's evidence tier (a weighted 0–100 score across human data, safety, replication and regulatory clarity), then by whether it's actually approved. This is a research reference, not medical or purchasing advice: an alternative sitting higher on evidence does not mean it's right, safe, or legal for any given use. Reviewed June 1, 2026.
PepCue keeps every compound, dose and lab in one private, provider-ready timeline, whichever one you land on.