The tricyclic antidepressant desipramine inhibits T3 import into primary neurons

Transport of thyroid hormones across the plasma membrane is required for binding to their nuclear receptors. Monocarboxylate transporter 8 (MCT8) is a plasma membrane thyroid hormone transport protein, which has recently gained much attention, since mutations in MCT8 are associated with severe mental retardation in patients afflicted with the Allan-Herndon-Dudley syndrome. MCT8 is expressed along the blood-brain-barrier and on central neurons. We have found that desipramine (DMI), a tricyclic antidepressant, acts as an inhibitor of thyroid hormone transport by MCT8. Uptake of 3,5,3'-triiodo-L-thyronine (T(3)) into primary cortical neurons could be blocked with desipramine as well as with the known, but unspecific, inhibitor bromosulphtalein (BSP). T(3) uptake by neurons derived from Mct8-deficient cells was not further decreased by DMI. In a heterologous expression system, both human MCT8 and its close homolog, MCT10, were sensitive to inhibition by DMI. Kinetic experiments demonstrated a non-competitive mode of inhibition. Numerous interactions between thyroid hormones, depressive symptoms, and antidepressant treatments have been reported in the literature. Our findings add to the evidence that antidepressant drugs may affect CNS thyroid hormone function.