How do psychostimulants enter the human brain? Analysis of the role of the proton-organic cation antiporter.
Biochemical pharmacology October 1, 2021 Alexandra Sachkova, David Alexander Doetsch, Ole Jensen et al. 11 citations
Many psychostimulants and hallucinogens are hydrophilic and positively charged, making it unclear how they cross the blood-brain barrier (BBB). A genetically uncharacterized proton-organic cation (H+/OC) antiporter at the BBB may mediate this transport. Using hCMEC/D3 cells, uptake of methylenedioxyamphetamines, amphetamines, and dimethyltryptamine (DMT) was strongly inhibited by imipramine and diphenhydramine, while cathine was weakly inhibited and mescaline not significantly. Exchange transport after preloading with diphenhydramine left only 1.9% to 7.8% of several compounds in cells, but mescaline showed no exchange. Except for mescaline, all tested psychostimulants were substrates of the H+/OC antiporter, highlighting the need to better characterize this transporter.