Serotonin–norepinephrine–dopamine Reuptake Inhibitor

A serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), or triple reuptake inhibitor (TRI), is a drug/ligand that simultaneously acts as a reuptake inhibitor for the monoamine neurotransmitters, serotonin (5-HT), norepinephrine (noradrenaline, NA) and dopamine (DA), by blocking the action of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT), respectively. This, in turn, leads to increased extracellular concentrations of these neurotransmitters and, therefore, an increase in serotonergic, noradrenergic or adrenergic, and dopaminergic neurotransmission. In this sense, to a degree, there is omnipresence in what these compounds do. This group of drugs/ligands are believed to work in much the same way as the nonselective monoamine releasers (E.G. 4-FA, PBA, and PAL-287), albeit through a differing mechanism of activity.

The exact chemical signature depends on the specific compound under consideration. In addition, there is the case of the nonselective MAOIs, including tranylcypromine and phenelzine, to consider. These also elevate the extracellular concentration of (and the amount of synaptic signaling of) monoaminergic neurotransmitters (i.e. 5-HT, NA and DA) in the CNS. Many of the substituted amphetamines also display MAOI activity, although they are reversible and not 'suicide inhibitors'.

Collectively, such compounds are often (somewhat disparagingly) referred to as 'dirty drugs' because they recruit a plurality of modes of activity. This label can be considered ambiguous in so-far as it could be interpreted as meaning that the chemical purity of the compounds is inadequate, when, in fact, this is not the point that is being labored. Bryan Roth argues that calling these drugs/ligands nonselective is not sufficient, and that they should instead be referred to as selectively–nonselective; this implies that there is a certain amount of deliberation involved, and it is not just a stochastic process.