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

It is shown that the tricyclic antidepressant drug doxepin (comprising 15% of the cis- and 85% of the trans-isomer) is a moderately potent competitive inhibitor of serotonin uptake in human blood platelets in vitro, with an inhibitory constant Ki of about 2 X 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 with 14C-serotonin was not affected by doxepin in concentrations up to 10(-6) M, but increased rapidly at concentrations above 10(-4) M.