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'''Triple releasing agent''' (also called a '''TRA''' or '''triple releaser''') is a informal term to describe a type of psychoactive substance which exerts its activity by inducing the release and increase in concentration of the three major central nervous [[monoamine]] neurotransmitters, [[serotonin]], [[norepinephrine]], and [[dopamine]] within the [[synapse]]s of various regions in the brain. In the field of neuropharmacology, they are more formally referred to as '''serotonin-norepinephrine-dopamine releasing agents (SNDRA)'''.{{citation needed}}
'''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 [[Euphoria|euphoriant]], [[entactogen]], and [[stimulant]] effects, and are almost exclusively encountered in the context of [[recreational drug use]].


In the context of [[psychonautics]] and [[recreational drug use]] triple releasing agents are typically associated with the ability to produce [[Euphoria|euphoriant]], [[entactogen]]ic, and [[stimulant|stimulating]] effects in a manner similar to [[MDMA]], [[MDA]], [[4-FA]] and other amphetamine-based compounds, with the serotonergic entactogenic aspects typically being the most prominent and desired effect.
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<ref>Chen, Z., & Skolnick, P. (2007). Triple uptake inhibitors: therapeutic potential in depression and beyond. Expert Opinion on Investigational Drugs, 16(9), 1365-1377. http://dx.doi.org/10.1517/13543784.16.9.1365</ref> 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 [[Appetite suppression|anorectics]].{{citation needed}} Other triple reuptake inhibitors see widespread use as [[recreational drug use|recreational drugs]], with [[cocaine]] being a prominent example.
 
A closely related type of substance is a '''triple reuptake inhibitor (TRI)''', which also produces an increase in synaptic concentrations of the above-mentioned monoamines, albeit through a different mechanism. Relative to triple releasing agents, triple reuptake inhibitors have a long history been investigated for various potential medical uses<ref>Chen, Z., & Skolnick, P. (2007). Triple uptake inhibitors: therapeutic potential in depression and beyond. Expert Opinion on Investigational Drugs, 16(9), 1365-1377. http://dx.doi.org/10.1517/13543784.16.9.1365</ref> 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 [[Appetite suppression|anorectics]].{{citation needed}}
 
Unlike triple releasing agents, the family of triple reuptake inhibitors used for the purposes of [[recreational drug use]] is extremely limited, with [[cocaine]] being perhaps the only prominent example.{{citation needed}}


==Neurotoxicity==
==Neurotoxicity==
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, plasmalemma and vesicular transporters, and the cell membrane, ultimately causing cell death as a result.{{citation needed}}
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}}
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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* [[Agonist]]
* [[Agonist]]
* [[Antagonist]]
* [[Antagonist]]
==External links==
*[[wikipedia:Serotonin-norepinephrine-dopamine releasing agent|Serotonin-norepinephrine-dopamine releasing agent (Wikipedia)]]


==References==
==References==
<references />
<references />
[[Category:Approval]]

Latest revision as of 18:35, 9 February 2020

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.

Neurotoxicity

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]

Examples

See also

References

  1. ↑ Chen, Z., & Skolnick, P. (2007). Triple uptake inhibitors: therapeutic potential in depression and beyond. Expert Opinion on Investigational Drugs, 16(9), 1365-1377. http://dx.doi.org/10.1517/13543784.16.9.1365
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