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The following section covers the peptides with the most substantive research behind their antidepressant properties, presented in order of evidence strength and mechanistic interest

Through several mechanisms, including direct interaction with SUR1 and membrane depolarization, intracellular calcium mobilization, and insulin granule priming modification, EPAC2 activation may promote the exocytosis of insulin granules [55, 56]

Cagrilintide, the second generation (2020s) Novo Nordisk took the Pramlintide concept and applied the same half-life extension strategy that they used with Semaglutide: Kept the proline substitutions (anti-amyloid) Added a C20 fatty diacid via a -Glu linker to a lysine residue, albumin binding Additionally stabilized the N- and C-terminal positions Result: Cagrilintide with a half-life of 6.6 days (vs 50 minutes for Pramlintide)

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Mass spectrometry confirms molecular weight matching expected values