Talk:Triple releasing agent

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Triple releasing agent (TRA), also known as a (serotonin-norepinephrine-dopamine releasing agent (SNDRA)), is a type of psychoactive substance that induces the release of four major central nervous system monoamine neurotransmitters, serotonin, norepinephrine, epinephrine, and dopamine, in the body and/or brain. Triple releasing agents are known to typically produce euphoriant, entactogen, and stimulant effects, and are almost exclusively encountered in the context of recreational drug use.

A closely related type of substance is a triple reuptake inhibitor (TRI), which also typically produce an increase in synaptic concentrations of the above-mentioned monoamines, albeit through a different mechanism. Unlike triple releasing agents, triple reuptake inhibitors have been investigated for various potential medical uses[1] and FDA approval has been granted for the use of one such compound as an antidepressant,[citation needed] and for the use of several others as anorectics.[citation needed] Other triple reuptake inhibitors see widespread use as recreational drugs, with cocaine being a prominent example.


Many releasing agents, notably many of those derived from amphetamine, have been found to be neurotoxic to serotonin and/or dopamine neurons via damage to axons and dendrites, enzymes, mitochondria, DNA, plasmalemmal and vesicular transporters, and the cell membrane, ultimately causing cell death as a result.[citation needed]

The neurotoxicity of some of these drugs is believed to be caused by oxidative stress induced by the generation of reactive oxygen species or free radicals, highly reactive particles that rip apart proteins and induce chain reactions of destruction. The free radicals are thought to be generated as byproducts when either the base compound or one or more of its metabolites are broken down by the enzymes monoamine oxidase (MAO-B) and/or cyclooxygenase (COX). It is thought hyperthermia and concurrent serotonin-dopamine release may also play a major role in augmenting damage.[citation needed]


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  1. Chen, Z., & Skolnick, P. (2007). Triple uptake inhibitors: therapeutic potential in depression and beyond. Expert Opinion on Investigational Drugs, 16(9), 1365-1377.