Serotonin-dopamine reuptake inhibitor



A serotonin-dopamine reuptake inhibitor (SDRI) is a drug that acts as a reuptake inhibitor for the monoamine neurotransmitters serotonin and dopamine by blocking the actions of the serotonin transporter (SERT) and dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of serotonin and dopamine and, therefore, an increase in serotonergic and dopaminergic neurotransmission.

Unlike the case of other combination monoamine reuptake inhibitors such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and norepinephrine-dopamine reuptake inhibitors (NDRIs), on account of the very similar chemical structures of their substrates, it is extraordinarily difficult to tease apart affinity for the DAT from the norepinephrine transporter (NET) and inhibit the reuptake of dopamine alone. As a result, selective dopamine reuptake inhibitors (DRIs) are rare, and comparably, SDRIs are even more so. In fact, only two SDRIs are well-established in research at present, which are RTI-83 and UWA-101, though other related compounds are known. However, UWA-101 may also possess some activity as a releasing agent, and if so, unlike RTI-83, it would not be an SDRI in the purest sense and would instead be an SDRA or serotonin-dopamine releasing agent (of which it would be the only one known to currently exist). Manning et al. presented two high-affinity MAT-ligands with good binding selectivity for SERT and DAT, namely the 4-indolyl and 1-naphthyl arylalkylamines ent-16b (Ki 0.82, 3.8, 4840 nM for SERT, DAT, NET) and ent-13b respectively.

For additional information on SRIs and DRIs, respectively, please refer to these articles: