A serotonin–dopamine releasing agent (SDRA) is a type of drug which induces the release of serotonin and dopamine in the body and/or brain. A closely related type of drug is a serotonin–dopamine reuptake inhibitor (SDRI).

Examples of SDRAs

A number of tryptamine derivatives have been found to act as SDRAs. One such agent is 5-chloro-αMT (PAL-542), which has been reported as having about 64-fold selectivity for dopamine release over norepinephrine release and about 3-fold selectivity for serotonin release over dopamine release, making it a highly selective and well-balanced SDRA. Another agent is 5-fluoro-αET (PAL-545), which has about 35-fold selectivity for dopamine release over norepinephrine release and about 4-fold selectivity for serotonin release over dopamine release. Though selective for inducing the release of serotonin and dopamine over norepinephrine, these agents are not selective monoamine releasers; they have all also been found to be potent agonists of the 5-HT2A receptor, and are likely to act as agonists of other serotonin receptors as well. In any case, they are the only known releaser scaffold that consistently release dopamine more potently than norepinephrine. Another tryptamine SDRA is BK-NM-AMT (α,N-dimethyl-β-ketotryptamine). It is the N-methyl and β-keto analogue of αMT. The drug is a cathinone-like tryptamine and can be thought of as the tryptamine analogue of methcathinone. Its EC50 values for monoamine release are 41.3nM for serotonin and 92.8nM for dopamine, whereas it only induced 55% release of norepinephrine at a concentration of 10μM. BK-NM-AMT has been described in a patent assigned to Tactogen and published in October 2024. 5-Halogenated derivatives of this drug, including BK-5F-NM-AMT, BK-5Cl-NM-AMT, and BK-5Br-NM-AMT, have also been described and patented. Like BK-NM-AMT, they induce serotonin and dopamine release. In contrast to many other tryptamines, these compounds are inactive as agonists of serotonin receptors including the 5-HT1, 5-HT2, and 5-HT3 receptors. In addition, unlike other α-alkyltryptamines like αMT, they are inactive as monoamine oxidase inhibitors (MAOIs). 3-Methoxymethcathinone (3-MeOMC) is a rare possible example of a phenethylamine (or rather cathinone) SDRA. Its EC50 values for monoamine release are 129nM for dopamine and 306nM for serotonin, whereas it only induced 68% release of norepinephrine at 10μM. However, in another publication, its EC50 for induction of norepinephrine release was reported and was 111nM.

Activity profiles