A TNU animation · Joe Christensen · pilot
SSRIs: The Replay
How a selective serotonin reuptake inhibitor works, from the real structure up. 2:19 · narrated · for Translational Neuropharmacology
What's real in it
- Every SERT shape is a deposited cryo-EM state (human SERT with serotonin: 7LIA → 7MGW → 7LI9 → 7LI6 → 7LI7). The motion between them is interpolated and labelled illustrative.
- Escitalopram's pose (central + allosteric site) is from the 2016 crystal structure (5I73). The 5-HT1A–Gi complex is 7E2Y.
- Brain: the fsaverage cortical surface, the MNI152 template, AAL3 raphe outlines, and the human SERT PET atlas (Beliveau et al. 2017, NRU Copenhagen).
- Every number on screen is cited to its primary source. K⁺ is shown as a model, since no structure resolves it.
Where a longer version could go
- Target engagement vs benefit: ~80% SERT occupancy at therapeutic doses, yet improvement unfolds over weeks.
- Exposure: CYP2C19 genotype and CPIC-guided dosing.
- Same target, other tissues: platelet SERT and bleeding risk.
- A third take: MDMA as a transported releaser, not a blocker.
- Drug design: the allosteric site, vortioxetine and vilazodone (9HCO, 2025).
Sources
- Structures: Yang & Gouaux, Sci Adv 2021 (7LIA, 7MGW, 7LI9, 7LI6, 7LI7) · Coleman, Green & Gouaux, Nature 2016 (5I73) · Xu et al., Nature 2021 (7E2Y)
- Brain and cells: Fischl et al. (fsaverage) · Fonov et al. (MNI152 2009a) · Rolls et al. 2020 (AAL3) · Beliveau et al., J Neurosci 2017 (SERT PET atlas, CC BY-NC-SA) · Ren et al., eLife 2019 · NeuroMorpho NMO_81052 (Chen 2017) · Gagnon & Parent, PLoS ONE 2014 · Sheu et al., Cell 2022 · Voisin et al. 2016
- History: Wong et al., Life Sci 1974 · Hyttel, Psychopharmacology 1977 · Blakely et al., Nature 1991 · Hoffman et al., Science 1991 · Blier & de Montigny, J Neurosci 1983
- Facts: Rudnick & Sandtner, J Gen Physiol 2019 · Kristensen et al., Pharmacol Rev 2011 · Hellsberg et al., PNAS 2024 · Owens et al., Biol Psychiatry 2001 · Bousman et al. (CPIC), Clin Pharmacol Ther 2023 · Meyer et al., Am J Psychiatry 2004 · Klein et al. 2007 · Zhang et al., Mol Psychiatry 2025
- Narration: ElevenLabs v4 (voice: George). Music: ElevenLabs Music. Rendered entirely in code from deposited coordinates and published data.