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Monoamine releasing agent

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"Releasing agent" redirects here. For mold release agents, see Release agent.
Amphetamine, the prototypical monoamine releasing agent, which induces the release of dopamine and norepinephrine.[1]

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitters and hence enhanced signaling by those neurotransmitters.[2][3][4][1][5] The monoamine neurotransmitters include serotonin, norepinephrine, and dopamine; monoamine releasing agents can induce the release of one or more of these neurotransmitters.[2][3][4][1][5]

Monoamine releasing agents work by reversing the direction of the monoamine transporters (MATs), including the serotonin transporter (SERT), norepinephrine transporter (NET), and/or dopamine transporter (DAT), causing them to promote efflux of non-vesicular cytoplasmic monoamine neurotransmitter rather than reuptake of synaptic monoamine neurotransmitter.[5][6][1][7] Many, but not all monoamine releasing agents, also reverse the direction of the vesicular monoamine transporter 2 (VMAT2), thereby additionally resulting in efflux of vesicular monoamine neurotransmitter into the cytoplasm.[5]

A variety of different classes of drugs induce their effects in the body and/or brain via the release of monoamine neurotransmitters.[2][3] These include psychostimulants and appetite suppressants acting as dopamine and norepinephrine releasers like amphetamine, methamphetamine, and phentermine; sympathomimetic agents acting as norepinephrine releasers like ephedrine and pseudoephedrine; non-stimulant appetite suppressants acting as serotonin releasers like fenfluramine and chlorphentermine; and entactogens acting as releasers of serotonin and/or other monoamines like MDMA.[2][3] Trace amines like phenethylamine and tryptamine, as well as the monoamine neurotransmitters themselves, are endogenous monoamine releasing agents.[2][3][4] It is thought that monoamine release by endogenous mediators may play some physiological regulatory role.[4]

MRAs must be distinguished from monoamine reuptake inhibitors (MRIs) and monoaminergic activity enhancers (MAEs), which similarly increase synaptic monoamine neurotransmitter levels and enhance monoaminergic signaling but work via distinct mechanisms.[5][1][8][9]

Types and selectivity

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MRAs can be classified by the monoamines they mainly release, although these drugs lie on a spectrum:[2][3][4][5]

The differences in selectivity of MRAs is the result of different affinities as substrates for the monoamine transporters, and thus differing ability to gain access into monoaminergic neurons and induce monoamine neurotransmitter release.

As of present, no selective DRAs are known. This is because it has proven extremely difficult to separate DAT affinity from NET affinity and retain releasing efficacy at the same time.[10] Several selective SDRAs, including tryptamine, (+)-α-ethyltryptamine (αET), 5-chloro-αMT, and 5-fluoro-αET, are known.[11][12] However, besides their serotonin release, these compounds additionally act as non-selective serotonin receptor agonists, including of the serotonin 5-HT2A receptor (with accompanying hallucinogenic effects), and some of them are known to act as monoamine oxidase inhibitors.[11][12]

Effects and uses

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MRAs can produce varying effects depending on their selectivity for inducing the release of different monoamine neurotransmitters.[3]

Selective SRAs such as chlorphentermine have been described as dysphoric and lethargic.[13][14] Less selective SRAs that also stimulate the release of dopamine, such as methylenedioxymethamphetamine (MDMA), are described as more pleasant, more reliably elevating mood and increasing energy and sociability.[15] SRAs have been used as appetite suppressants and as entactogens. They have also been proposed for use as more effective antidepressants and anxiolytics than selective serotonin reuptake inhibitors (SSRIs) because they can produce much larger increases in serotonin levels in comparison.[16]

DRAs, usually non-selective for both norepinephrine and dopamine, have psychostimulant effects, causing an increase in energy, motivation, elevated mood, and euphoria.[17] Other variables can significantly affect the subjective effects, such as infusion rate (increasing positive effects of DRAs) and psychological expectancy effects.[18] They are used in the treatment of attention deficit hyperactivity disorder (ADHD), as appetite suppressants, wakefulness-promoting agents, to improve motivation, and are drugs of recreational use and misuse.

Selective NRAs are minimally psychoactive, but as demonstrated by ephedrine, may be distinguished from placebo, and may trends towards liking.[19] They may also be performance-enhancing,[20] in contrast to reboxetine which is solely a norepinephrine reuptake inhibitor.[21][22] In addition to their central effects, NRAs produce peripheral sympathomimetic effects like increased heart rate, blood pressure, and force of heart contractions. They are used as nasal decongestants and bronchodilators, but have also seen use as wakefulness-promoting agents, appetite suppressants, and antihypotensive agents. They have additionally seen use as performance-enhancing drugs, for instance in sports.

Mechanism of action

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MRAs cause the release of monoamine neurotransmitters by various complex mechanisms of action. They may enter the presynaptic neuron primarily via plasma membrane transporters, such as the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT). Some, such as exogenous phenethylamine, amphetamine, and methamphetamine, can also diffuse directly across the cell membrane to varying degrees. Once inside the presynaptic neuron, they may inhibit the reuptake of monoamine neurotransmitters through vesicular monoamine transporter 2 (VMAT2) and release the neurotransmitters stores of synaptic vesicles into the cytoplasm by inducing reverse transport at VMAT2. MRAs can also bind to the intracellular receptor TAAR1 as agonists, which triggers a phosphorylation cascade via protein kinases that results in the phosphorylation of monoamine transporters located at the plasma membrane (i.e., the dopamine transporter, norepinephrine transporter, and serotonin transporter); upon phosphorylation, these transporters transport monoamines in reverse (i.e., they move monoamines from the neuronal cytoplasm into the synaptic cleft).[23] The combined effects of MRAs at VMAT2 and TAAR1 result in the release of neurotransmitters out of synaptic vesicles and the cell cytoplasm into the synaptic cleft where they bind to their associated presynaptic autoreceptors and postsynaptic receptors. Certain MRAs interact with other presynaptic intracellular receptors which promote monoamine neurotransmission as well (e.g., methamphetamine is also an agonist at σ1 receptor).

In spite of findings that TAAR1 activation by amphetamines can reverse the monoamine transporters and mediate monoamine release however,[23][24][25][26] major literature reviews on monoamine releasing agents by experts like Richard B. Rothman and David J. Heal state that the nature of monoamine transport reversal is not well understood and/or do not mention TAAR1 activation.[5][6][1][7] Moreover, amphetamines continue to produce psychostimulant-like effects and induction of dopamine and norepinephrine release in TAAR1 knockout mice.[23][27][28][29][30] In fact, TAAR1 knockout mice are supersensitive to the effects of amphetamines and TAAR1 activation appears to inhibit the striatal dopaminergic effects of psychostimulants.[23][28][27][29][30] Additionally, many substrate-type MRAs that do not bind to and/or activate the (human) TAAR1 are known, including most cathinones, ephedrine, 4-methylamphetamine, and 4-methylaminorex derivatives, among others.[31][32][33][34]

There is a constrained and relatively small molecular size requirement for compounds to act as monoamine releasing agents.[5] This is because they must be small enough to serve as substrates of the monoamine transporters and thereby be transported inside of monoaminergic neurons by these proteins, in turn allowing them to induce monoamine neurotransmitter release.[5] Compounds with chemical features extending beyond the size constraints for releasers will instead act as partial releasers, reuptake inhibitors, or be inactive.[5] Partial releasers show reduced maximal efficacy in releasing monoamine neurotransmitters compared to conventional full releasers.[5]

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DAT "inverse agonists"

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Dopamine reuptake inhibitors (DRIs) have been grouped into two types, typical or conventional DRIs like cocaine, WIN-35428 (β-CFT), and methylphenidate that produce potent psychostimulant, euphoric, and reinforcing effects, and atypical DRIs like vanoxerine (GBR-12909), modafinil, benztropine, and bupropion, which do not produce such effects or have greatly reduced such effects.[7][6][5][35] It has been proposed that typical DRIs may not actually be acting primarily as DRIs but rather as dopamine releasing agents (DRAs) via mechanisms distinct from conventional substrate-type DRAs like amphetamines.[7] A variety of different pieces of evidence support this hypothesis and help to explain otherwise confusing findings.[7] Under this model, typical cocaine-like DRIs have been referred to with the new label of dopamine transporter (DAT) "inverse agonists" to distinguish them from conventional substrate-type DRAs.[7] An alternative theory is that typical DRIs and atypical DRIs stabilize the DAT in different conformations, with typical DRIs resulting in an outward-facing open conformation that produces differing pharmacological effects from those of atypical DRIs.[6][5][35][36]

Monoaminergic activity enhancers

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Some MRAs, like the amphetamines amphetamine and methamphetamine, as well as trace amines like phenethylamine, tryptamine, and tyramine, are additionally monoaminergic activity enhancers (MAEs).[8][9][37] That is, they induce the action potential-mediated release of monoamine neurotransmitters (in contrast to MRAs, which induced uncontrolled monoamine release independent of neuronal firing).[8][9][37] They are usually active as MAEs at much lower concentrations than those at which they induce monoamine release.[8][9][37] The MAE actions of MAEs may be mediated by TAAR1 agonism, which has likewise been implicated in monoamine-releasing actions.[38][39] MAEs without concomitant potent monoamine-releasing actions, like selegiline (L-deprenyl), phenylpropylaminopentane (PPAP), and benzofuranylpropylaminopentane (BPAP), have been developed.[8][9]

Endogenous MRAs

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A number of endogenous compounds are known to act as MRAs.[4][40][41][11][5] These include the monoamine neurotransmitters dopamine (an NDRA),[40] norepinephrine (an NDRA),[40] and serotonin (an SRA) themselves,[40] as well as the trace amines phenethylamine (an NDRA),[5][37][42][43] tryptamine (an SDRA or imbalanced SNDRA),[41][11] and tyramine (an NDRA).[40][4] Synthetic MRAs are substantially based on structural modification of these endogenous compounds, most prominently including the substituted phenethylamines and substituted tryptamines.[40][2][3][41][44][45][46]

Release of monoamine neurotransmitters by themselves, for instance in the cases of serotonin, norepinephrine, and dopamine, has been referred to as "self-release".[4] The physiological significance of the findings that monoamine neurotransmitters can act as releasing agents of themselves is unclear.[4] However, it could imply that efflux is a common neurotransmitter regulatory mechanism that can be induced by any transporter substrate.[4]

It is possible monoamine neurotransmitter self-release could be a protective mechanism.[4] It is notable in this regard that intracellular non-vesicular or cytoplasmic dopamine is toxic to neurons and that the vesicular monoamine transporter 2 (VMAT2) is neuroprotective by packaging this dopamine into synaptic vesicles.[47][48][49] Along similar lines, monoamine releasing agents induce the efflux of non-vesicular monoamine neurotransmitter and thereby move cytoplasmic neurotransmitter into the extracellular space.[5] However, many, though not all, monoamine releasing agents also act as VMAT2 inhibitors and reversers and hence concomitantly induce the release of vesicular monoamine neurotransmitter into the cytoplasm.[5]

Monoaminergic neurotoxicity

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Main article: Monoaminergic neurotoxin

Some MRAs have been found to act as monoaminergic neurotoxins and hence to produce long-lasting damage to monoaminergic neurons.[50][51] Examples include dopaminergic neurotoxicity with amphetamine and methamphetamine and serotonergic neurotoxicity with methylenedioxymethamphetamine (MDMA).[50][51] Amphetamine may produce significant dopaminergic neurotoxicity even at therapeutic doses.[52][53][54][55][56][57] However, clinical doses of amphetamine producing neurotoxicity is controversial and disputed.[58][52][54] In contrast to amphetamines, monoamine reuptake inhibitors like methylphenidate lack apparent neurotoxic effects.[52]

Analogues of MDMA with retained MRA activity but reduced or no serotonergic neurotoxicity, like 5,6-methylenedioxy-2-aminoindane (MDAI) and 5-iodo-2-aminoindane (5-IAI), have been developed.[59][60] Certain drugs have been found to block the neurotoxicity of MRAs in animals.[51] For instance, the selective MAO-B inhibitor selegiline has been found to prevent the serotonergic neurotoxicity of MDMA in rodents.[51]

Activity profiles

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See also: Monoamine reuptake inhibitor § Binding profiles
Activity profiles of MRAs (EC50, nM)[2][3]
Compound 5-HTTooltip Serotonin NETooltip Norepinephrine DATooltip Dopamine Type Class Ref
2-Aminoindane >10000 86 439 NDRA Aminoindane [61]
2-APBT 8.9 21.6 38.6 SNDRA Aminopropylbenzothiophene [62]
2C-E >100000 >100000 >100000 IA Phenethylamine [63]
2C-I >100000 >100000 >100000 IA Phenethylamine [63]
3-APBT 21.9 13.4 21.7 SNDRA Aminopropylbenzothiophene [62]
3-Chloroamphetamine ND 9.4 11.8 ND Amphetamine [64][4]
3-Chloromethcathinone 211 19 26 SNDRA Cathinone [5]
3-Fluoroamphetamine 1937 16.1 24.2 NDRA Amphetamine [65][4]
3-Methoxyamphetamine ND 58.0 103 ND Amphetamine [4]
3-Methoxy-4-hydroxymethamphetamine (HMMA) 589 625 607–2884 SNDRA Amphetamine [4][66]
3-Methoxymethcathinone (3-MeOMC) 306 ND (68% at 10 μM) 129 SDRA Cathinone [67]
3-Methylamphetamine 218 18.3 33.3 NDRA Amphetamine [65][64][4]
3-Methylmethcathinone 292 27 70 SNDRA Cathinone [5]
3,4-Dihydroxyamphetamine (HHA) ND 33 3485 ND Amphetamine [4]
3,4-Dihydroxymethamphetamine (HHMA) ND 77 1729 ND Amphetamine [4]
4-APBT 21.2 46.2 66.6 SNDRA Aminopropylbenzothiophene [62]
4-Chloroamphetamine ND 23.5 68.5 SNDRA Amphetamine [64][4]
4-Fluoroamphetamine 730–939 28.0–37 51.5–200 NDRA Amphetamine [65][63][64][4]
4-Hydroxy-3-methoxyamphetamine (HMA) 897 694 1450–3423 ND Amphetamine [4][66]
4-Methoxyamphetamine ND 166 867 ND Amphetamine [4]
cis-4-Methylaminorex 53.2 4.8 1.7 NDRA Aminorex [68]
4-Methylamphetamine 53.4 22.2 44.1 SNDRA Amphetamine [65][64][4]
4-Methylphenethylamine ND ND 271 ND Phenethylamine [5]
4-Methylthiomethamphetamine 21 ND ND ND Amphetamine [69]
4,4'-Dimethylaminorex ND ND ND SNDRA Aminorex ND
  cis-4,4'-Dimethylaminorex 17.7–18.5 11.8–26.9 8.6–10.9 SNDRA Aminorex [68][70]
  trans-4,4'-Dimethylaminorex 59.9 31.6 24.4 SNDRA Aminorex [70]
5-APB 19 21 31 SNDRA Amphetamine [71]
5-APBT 10.3 38.4 92.8 SNDRA Aminopropylbenzothiophene [62]
5-(2-Aminopropyl)indole (5-IT) 28–104.8 13.3–79 12.9–173 SNDRA Amphetamine [12][72]
  (R)-5-(2-Aminopropyl)indole 177 81 1062 SNRA Amphetamine [12]
  (S)-5-(2-Aminopropyl)indole ND ND ND SNDRA Amphetamine ND
5-Chloro-αMT 16 3434 54 SDRA Tryptamine [11][12]
5-Fluoro-αET 36.6 5334 150 SDRA Tryptamine [11]
5-Fluoro-αMT 19 126 32 SNDRA Tryptamine [12]
5-MABB ND ND ND ND Amphetamine [73][74]
  (S)-5-MABB 31 158 210 SNDRA Amphetamine [73][74]
  (R)-5-MABB 49 850 IA SRA Amphetamine [73][74]
5-MAPB (5-MBPB) 64–90 24 41–459 SNDRA Amphetamine [71][75]
  (S)-5-MAPB 67 ND 258 ND Amphetamine [75]
  (R)-5-MAPB 184 ND 1951 ND Amphetamine [75]
5-MeO-αMT 460 8900 1500 SNDRA Tryptamine [63]
5-MeO-AI 134 861 2646 SNRA Aminoindane [61]
5-MeO-DMT >100000 >100000 >100000 IA Tryptamine [63]
6-APB 36 14 10 SNDRA Amphetamine [71]
6-APBT 10.7 13.6 7.2 SNDRA Aminopropylbenzothiophene [62]
6-(2-Aminopropyl)indole (6-IT) 19.9 25.6 164.0 SNDRA Amphetamine [72]
6-Chloroamphetamine ND 19.1 62.4 ND Amphetamine [4]
6-Fluoroamphetamine ND 24.1 38.1 ND Amphetamine [4]
6-MABB (6-MBPB) ND ND ND ND Amphetamine [73][74]
  (R)-6-MABB 172 227 IA SNRA Amphetamine [73][74]
  (S)-6-MABB 54 77 41 SNDRA Amphetamine [73][74]
6-MAPB 33 14 20 SNDRA Amphetamine [71]
6-Methoxyamphetamine ND 473 1478 ND Amphetamine [4]
6-Methylamphetamine ND 37 127 ND Amphetamine [4]
7-APBT 36.9 28.5 16.8 SNDRA Aminopropylbenzothiophene [62]
α-Ethyltryptamine 23.2 640 232 SDRA Tryptamine [11]
α-Methyltryptamine 21.7–68 79–112 78.6–180 SNDRA Tryptamine [63][11]
Amfepramone (diethylpropion) >10000 >10000 >10000 PD Cathinone [76]
Aminorex 193–414 15.1–26.4 9.1–49.4 SNDRA Aminorex [40][68][4]
Amphetamine ND ND ND NDRA Amphetamine ND
  D-Amphetamine 698–1765 6.6–10.2 5.8–24.8 NDRA Amphetamine [40][77][4]
  L-Amphetamine ND 9.5 27.7 NDRA Amphetamine [64][4]
BDB 180 540 2,300 NDRA Amphetamine [63]
Benzylpiperazine ≥6050 62–68 175–600 NDRA Arylpiperazine [63][78][3][4]
BK-NM-AMT 41.3 ND (55% at 10 μM) 92.8 SDRA Tryptamine [67][79]
BK-5F-NM-AMT 190 ND 620 ND Tryptamine [80]
BK-5Cl-NM-AMT 200 ND 865 ND Tryptamine [80]
BK-5Br-NM-AMT 295 ND 2100 ND Tryptamine [80]
Bufotenin 30.5 >10000 >10000 SRA Tryptamine [41]
Butylamphetamine ND ND IA ND Amphetamine [5]
Cathinone 6100 23.6 83.1 NDRA Cathinone [4][67]
  D-Cathinone ND ND ND NRA Cathinone ND
  L-Cathinone 2366 12.4 18.5 NDRA Cathinone [81]
Chlorphentermine 30.9 >10000 2650 SRA Amphetamine [40]
DMPP 26 56 1207 SNRA Arylpiperazine [69]
DMT 114 4166 >10000 SRA Tryptamine [41]
Dopamine >10000 (RI) 66.2 86.9 NDRA Phenethylamine [40][4]
DPT >100000 >100000 >100000 IA Tryptamine [63][41]
EDMA 117 325 597 SNDRA Amphetamine [82]
EDMC 347 327 496 SNDRA Cathinone [82]
Ephedrine (racephedrine) ND ND ND NDRA Cathinol ND
  D-Ephedrine (ephedrine) >10000 43.1–72.4 236–1350 NDRA Cathinol [40][4]
  L-Ephedrine >10000 218 2104 NRA Cathinol [40][81]
Epinephrine ND ND ND NDRA Phenethylamine ND
Ethcathinone 2118 99.3 >1000 (RI) NRA Cathinone [76][4]
Ethylamphetamine ND ND 88.5 ND Amphetamine [5]
Fenfluramine 79.3–108 739 >10000 (RI) SRA Amphetamine [40][83][84][4]
  D-Fenfluramine 51.7 302 >10000 SNRA Amphetamine [40][83]
  L-Fenfluramine 147 >10000 >10000 SRA Amphetamine [83][85]
MBDB 540 3300 >100000 SNRA Amphetamine [63]
mCPP 28–38.1 ≥1400 63000 SRA Arylpiperazine [63][85][86]
MDA 160–162 47–108 106–190 SNDRA Amphetamine [84][4][71]
  (R)-MDA 310 290 900 SNDRA Amphetamine [84][4]
  (S)-MDA 100 50.0 98.5 SNDRA Amphetamine [84][4]
MDAI 114 117 1334 SNRA Aminoindane [61]
MDEA 47 2608 622 SNDRA Amphetamine [69]
  (R)-MDEA 52 651 507 SNDRA Amphetamine [69]
  (S)-MDEA 465 RI RI SRA Amphetamine [69]
MDMA 50–85 54–110 51–278 SNDRA Amphetamine [40][87][72][84][4][71]
  (R)-MDMA 340 560 3700 SNDRA Amphetamine [84][4]
  (S)-MDMA 74 136 142 SNDRA Amphetamine [84][4]
MDMAR ND ND ND SNDRA Aminorex ND
  cis-MDMAR 43.9 14.8 10.2 SNDRA Aminorex [70]
  trans-MDMAR 73.4 38.9 36.2 SNDRA Aminorex [70]
Mephedrone 118.3–122 58–62.7 49.1–51 SNDRA Cathinone [87][77]
Methamnetamine 13 34 10 SNDRA Amphetamine [69]
Methamphetamine ND ND ND NDRA Amphetamine ND
  D-Methamphetamine 736–1291.7 12.3–13.8 8.5–24.5 NDRA Amphetamine [40][87][4]
  L-Methamphetamine 4640 28.5 416 NRA Amphetamine [40][4]
Methcathinone ND 22.4 49.9 NDRA Cathinone [4]
  D-Methcathinone ND ND ND NRA Cathinone ND
  L-Methcathinone 1772 13.1 14.8 NDRA Cathinone [81]
Methylone 234–242.1 140–152.3 117–133.0 SNDRA Cathinone [87][77]
MMAI 31 3101 >10000 SRA Aminoindane [61]
Naphthylisopropylamine 3.4 11.1 12.6 SNDRA Amphetamine [88][4]
Norephedrine (phenylpropanolamine) ND ND ND NDRA Cathinol ND
  D-Norephedrine >10000 42.1 302 NDRA Cathinol [81]
  L-Norephedrine >10000 137 1371 NRA Cathinol [81]
Norepinephrine >10000 164 869 NDRA Phenethylamine [40][4]
Norfenfluramine 104 168–170 1900–1925 SNRA Amphetamine [83][84]
  (+)-Norfenfluramine 59.3 72.7 924 SNRA Amphetamine [83]
  (–)-Norfenfluramine 287 474 >10000 SNRA Amphetamine [83]
Norpropylhexedrine ND ND ND NDRA Cyclohexethylamine ND
Norpseudoephedrine ND ND ND NDRA Cathinol ND
  D-Norpseudoephedrine (cathine) >10000 15.0 68.3 NDRA Cathinol [81]
  L-Norpseudoephedrine >10000 30.1 294 NDRA Cathinol [81]
oMPP 175 39.1 296–542 SNDRA Arylpiperazine [89][5]
PAL-738 23 65 58 SNDRA Phenylmorpholine [69]
PAL-874 >10000 305 688 NDRA Phenylbutynamine [69]
Phenacylamine (β-ketophenethylamine) >10000 ND 208 ND Phenethylamine [5][67]
Phendimetrazine >100000 >10000 >10000 PD Phenylmorpholine [90][4]
Phenethylamine >10000 10.9 39.5 NDRA Phenethylamine [5][64][4]
Phenmetrazine 7765 50.4 131 NDRA Phenylmorpholine [90][4]
Phentermine 3511 39.4 262 NDRA Amphetamine [40][4]
Phenylalaninol ND ND ND ND Amphetamine ND
  D-Phenylalaninol >10000 106 1355 NRA Amphetamine [89]
  L-Phenylalaninol ND ND ND ND Amphetamine ND
Phenylisobutylamine ND ND 225 ND Amphetamine [5]
Phenylpropylamine ND 222 1491 NDRA Phenylpropylamine [64][4]
pMPP 3200 1500 11000 SNRA Arylpiperazine [63]
pNPP 43 >10000 >10000 SRA Arylpiperazine [69]
Propylamphetamine ND ND RI (1013) ND Amphetamine [5]
Propylhexedrine ND ND ND NDRA Cyclohexethylamine ND
Pseudoephedrine (racemic pseudoephedrine) ND ND ND NDRA Cathinol ND
  D-Pseudoephedrine >10000 4092 9125 NDRA Cathinol [81]
  L-Pseudoephedrine (pseudoephedrine) >10000 224 1988 NRA Cathinol [81]
Pseudophenmetrazine >10000 514 RI NRA Phenylmorpholine [90]
Psilocin 561 >10000 >10000 SRA Tryptamine [69][41]
Serotonin 44.4 >10000 (RI) ≥1960 SRA Tryptamine [40][4]
TFMCPP 33 >10000 >10000 SRA Arylpiperazine [69]
TFMPP 121 >10000 >10000 SRA Arylpiperazine [78][4]
Trimethoxyamphetamine 16000 >100000 >100000 IA Amphetamine [63]
Tryptamine 32.6 716 164 SDRA Tryptamine [41][11]
Tyramine 2775 40.6 119 NDRA Phenethylamine [40][4]
Notes: The smaller the value, the more strongly the substance releases the neurotransmitter.

References

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Further reading

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