Antidepressants enter cells, organelles, and membranes.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology January 1, 2024 Zack Blumenfeld, Kallol Bera, Eero Castrén et al. 10 citations
Many antidepressants work by entering cells and binding to targets inside the cytoplasm or organelles, contrary to the traditional view that they act only at extracellular sites on cell surface proteins. The ability of a drug to cross membranes depends on its charge and lipid solubility, described by parameters LogP, pKa, and LogD at pH 7.4. Some antidepressants have an unusually large volume of distribution, reflecting both binding to membranes and trapping inside acidic organelles. For SSRIs and SNRIs, the exact cellular compartment where they engage their target transporters remains unknown. Rapidly acting antidepressants like ketamine and psychedelics also rely on these intracellular mechanisms, an area termed location-biased or inside-out pharmacology.