Effect of doxepin on uptake and efflux of serotonin in human blood patelets in vitro

Abstract

It is shown that the tricyclic antidepressant drug doxepin (comprising 15% of thecis- and 85% of thetrans-isomer) is a moderately potent competitive inhibitor of serotonin uptake in human blood platelets in vitro, with an inhibitory constantK_i of about 2×10^-7 M. The inhibitory effect was 6 times stronger in an artificial, protein-free medium than in diluted plasma, corresponding to about 85% protein binding. The efflux of serotonin from platelets preloaded with¹⁴C-serotonin was not affected by doxepin in concentrations up to 10^-6 M, but increased rapidly at concentrations above 10^-4 M.