Monoamine releasing agent
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A monoamine releasing agent (MRA), or simply monoamine releaser, is a
Types of MRAs
MRAS can be classified by the monoamines they mainly release, although these drugs lie on a spectrum.
- Selective for one neurotransmitter
- Serotonin releasing agent (SRA)
- Norepinephrine releasing agent (NRA)
- Dopamine releasing agent (DRA)
- Non-selective, releasing two or more neurotransmitters
Mechanism of action
MRAs cause the
Effects
Monoamine releasing agents can have a wide variety of effects depending upon their selectivity for monoamines. Selective serotonin releasing agents such as fenfluramine and related compounds are described as dysphoric and lethargic in lower doses, and in higher doses some hallucinogenic effects have been reported.[2][3] Less selective serotonergic agents that stimulate an efflux in dopamine, such as MDMA are described as more pleasant, increasing energy, sociability and elevating mood.[4] Dopamine releasing agents, usually selective for both norepinephrine and dopamine have psychostimulant effect, causing an increase in energy, and elevated mood.[5] Other variables can significantly affect the subjective effects, such as infusion rate(increasing positive effects of cocaine), and expectancy.[6] Selectively noradrenergic drugs are minimally psychoactive, but as demonstrated by ephedrine may be distinguished from placebo, and trends towards liking.[7] They may also be ergogenic,[8] in contrast to reboxetine which is solely a reuptake inhibitor.[9][10]
Selectivity
MRAs act to varying extents on serotonin, norepinephrine, and dopamine. Some induce the release of all three neurotransmitters to a similar degree, like
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.
Activity profiles
Compound | 5-HT | NE | DA | Type | Class | Ref |
---|---|---|---|---|---|---|
2C-E | >100000 | >100000 | >100000 | IA | Phenethylamine | [15] |
2C-I | >100000 | >100000 | >100000 | IA | Phenethylamine | [15] |
3-Chloromethcathinone | ND | ND | 46.8 | ND | Cathinone | [16] |
3-Fluoroamphetamine | 1937 | 16.1 | 24.2 | NDRA | Amphetamine | [17] |
3-Methylamphetamine | 218 | 18.3 | 33.3 | NDRA | Amphetamine | [17] |
4-Fluoroamphetamine | 730–939 | 28.0–37 | 51.5–200 | NDRA | Amphetamine | [17][15] |
cis-4-Methylaminorex | 53.2 | 4.8 | 1.7 | NDRA | Aminorex | [18] |
4-Methylamphetamine | 53.4 | 22.2 | 44.1 | SNDRA | Amphetamine | [17] |
4-Methylphenethylamine | ND | ND | 271 | ND | Phenethylamine | [16] |
4-Methylthiomethamphetamine | 21 | ND | ND | ND | Amphetamine | [19] |
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 | [18][20] |
''trans''-4,4'-Dimethylaminorex | 59.9 | 31.6 | 24.4 | SNDRA | Aminorex | [20] |
5-(2-Aminopropyl)indole |
28–104.8 | 13.3–79 | 12.9–173 | SNDRA | Amphetamine | [12][21] |
(''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 | [12] |
5-Fluoro-αMT |
19 | 126 | 32 | SNDRA | Tryptamine | [12] |
5-MeO-αMT |
460 | 8900 | 1500 | SNDRA | Tryptamine | [15] |
5-MeO-DMT | >100000 | >100000 | >100000 | IA | Tryptamine | [15] |
6-(2-Aminopropyl)indole | 19.9 | 25.6 | 164.0 | SNDRA | Amphetamine | [21] |
Adderall | ND | ND | ND | NDRA | Amphetamine | ND |
α-Methyltryptamine | 68 | 79 | 180 | SNDRA | Tryptamine | [15] |
Amfepramone (diethylpropion) | >10000 | >10000 | >10000 | PD | Cathinone | [22] |
Aminorex | 193–414 | 15.1–26.4 | 9.1–49.4 | SNDRA | Aminorex | [23][18] |
Amphetamine | ND | ND | ND | NDRA | Amphetamine | ND |
D-Amphetamine | 698–1765 | 6.6–7.2 | 5.8–24.8 | NDRA | Amphetamine | [23][24] |
L-Amphetamine | ND | ND | ND | NRA | Amphetamine | ND |
β-Ketophenethylamine | ND | ND | 208 | ND | Phenethylamine | [16] |
BDB |
180 | 540 | 2,300 | NDRA | Amphetamine | [15] |
Benzylpiperazine | ≥6050 | 62–68 | 175–600 | NDRA | Arylpiperazine | [15][25][14] |
Butylamphetamine | ND | ND | IA | ND | Amphetamine | [16] |
Cathinone | ND | ND | ND | NDRA | Cathinone | ND |
D-Cathinone | ND | ND | ND | NRA | Cathinone | ND |
L-Cathinone | 2366 | 12.4 | 18.5 | NDRA | Cathinone | [26] |
Chlorphentermine | 30.9 | >10000 | 2650 | SRA | Amphetamine | [23] |
DMPP | 26 | 56 | 1207 | SNRA | Arylpiperazine | [19] |
Dopamine | >10000 | 66.2 | 86.9 | NDRA | Phenethylamine | [23] |
DPT | >100000 | >100000 | >100000 | IA | Tryptamine | [15] |
Ephedrine | ND | ND | ND | NDRA | Cathinol |
ND |
D-Ephedrine | >10000 | 43.1–72.4 | 236–1350 | NDRA | Cathinol | [23] |
L-Ephedrine | >10000 | 218 | 2104 | NRA | Cathinol | [23][26] |
Epinephrine |
ND | ND | ND | NDRA | Phenethylamine | ND |
Ethcathinone | 2118 | 99.3 | >1000 | NRA | Cathinone | [22] |
Ethylamphetamine |
ND | ND | 296 | ND | Amphetamine | [16] |
Fenfluramine | 79.3–108 | 739 | >10000 | SRA | Amphetamine | [23][27][28] |
D-Fenfluramine | 51.7 | 302 | >10000 | SNRA | Amphetamine | [23][27] |
L-Fenfluramine |
147 | >10000 | >10000 | SRA | Amphetamine | [27][29] |
MBDB |
540 | 3300 | >100,000 | SNRA | Amphetamine | [15] |
mCPP | 28–38.1 | ≥1400 | 63000 | SRA | Arylpiperazine | [15][29][30] |
MDA |
160 | 108 | 190 | SNDRA | Amphetamine | [28] |
(''R'')-MDA | 310 | 290 | 900 | SNDRA | Amphetamine | [28] |
(''S'')-MDA | 100 | 50 | 98 | SNDRA | Amphetamine | [28] |
MDEA |
47 | 2608 | 622 | SNDRA | Amphetamine | [19] |
(''R'')-MDEA | 52 | 651 | 507 | SNDRA | Amphetamine | [19] |
(''S'')-MDEA | 465 | RI | RI | SRA | Amphetamine | [19] |
MDMA |
49.6–72 | 54.1–110 | 51.2–278 | SNDRA | Amphetamine | [23][31][21][28] |
(''R'')-MDMA | 340 | 560 | 3700 | SNDRA | Amphetamine | [28] |
(''S'')-MDMA | 74 | 136 | 142 | SNDRA | Amphetamine | [28] |
MDMAR | ND | ND | ND | SNDRA | Aminorex | ND |
''cis''-MDMAR | 43.9 | 14.8 | 10.2 | SNDRA | Aminorex | [20] |
''trans''-MDMAR | 73.4 | 38.9 | 36.2 | SNDRA | Aminorex | [20] |
Mephedrone | 118.3–122 | 58–62.7 | 49.1–51 | SNDRA | Cathinone | [31][24] |
Methamnetamine | 13 | 34 | 10 | SNDRA | Amphetamine | [19] |
Methamphetamine | ND | ND | ND | NDRA | Amphetamine | ND |
D-Methamphetamine |
736–1291.7 | 12.3–13.8 | 8.5–24.5 | NDRA | Amphetamine | [23][31] |
L-Methamphetamine | 4640 | 28.5 | 416 | NRA | Amphetamine | [23] |
Methcathinone | ND | ND | ND | NDRA | Cathinone | ND |
D-Methcathinone | ND | ND | ND | NRA | Cathinone | ND |
L-Methcathinone | 1772 | 13.1 | 14.8 | NDRA | Cathinone | [26] |
Methylone | 234–242.1 | 140–152.3 | 117–133.0 | SNDRA | Cathinone | [31][24] |
Naphthylisopropylamine |
3.4 | 11.1 | 12.6 | SNDRA | Amphetamine | [32] |
Norephedrine |
ND | ND | ND | NDRA | Cathinol | ND |
D-Norephedrine | >10000 | 42.1 | 302 | NDRA | Cathinol | [26] |
L-Norephedrine (phenylpropanolamine) | >10000 | 137 | 1371 | NRA | Cathinol | [26] |
Norepinephrine | >10000 | 164 | 869 | NDRA | Phenethylamine | [23] |
Norfenfluramine | 104 | 168–170 | 1900–1925 | SNRA | Amphetamine | [27][28] |
Norpropylhexedrine | ND | ND | ND | NDRA | Cyclohexethylamine | ND |
D-Norpropylhexedrine | ND | ND | ND | NRA | Cyclohexethylamine | ND |
L-Norpropylhexedrine | ND | ND | ND | NDRA | Cyclohexethylamine | ND |
Norpseudoephedrine | ND | ND | ND | NDRA | Cathinol | ND |
D-Norpseudoephedrine (cathine) | >10000 | 15.0 | 68.3 | NDRA | Cathinol | [26] |
L-Norpseudoephedrine | >10000 | 30.1 | 294 | NDRA | Cathinol | [26] |
oMPP | 175 | 39.1 | 296–542 | SNDRA | Arylpiperazine | [33][16] |
PAL-738 | 23 | 65 | 58 | SNDRA | Phenylmorpholine | [19] |
Phenethylamine | ND | ND | 39.5 | NDRA | Phenethylamine | [16] |
Phendimetrazine | >100000 | >10000 | >10000 | PD | Phenylmorpholine | [34] |
Phenmetrazine | 7765 | 50.4 | 131 | NDRA | Phenylmorpholine | [34] |
Phentermine | 3511 | 39.4 | 262 | NDRA | Amphetamine | [23] |
Phenylalaninol | ND | ND | ND | ND | Amphetamine | ND |
D-Phenylalaninol | >10000 | 106 | 1355 | NRA | Amphetamine | [33] |
L-Phenylalaninol | ND | ND | ND | ND | Amphetamine | ND |
Phenylisobutylamine | ND | ND | 225 | ND | Amphetamine | [16] |
pMPP | 3200 | 1500 | 11000 | SNRA | Arylpiperazine | [15] |
pNPP | 43 | >10000 | >10000 | SRA | Arylpiperazine | [19] |
Propylamphetamine | ND | ND | RI (1013) | ND | Amphetamine | [16] |
Propylhexedrine | ND | ND | ND | NDRA | Cyclohexethylamine | ND |
D-Propylhexedrine | ND | ND | ND | NRA | Cyclohexethylamine | ND |
L-Propylhexedrine | ND | ND | ND | NDRA | Cyclohexethylamine | ND |
Pseudoephedrine | ND | ND | ND | NDRA | Cathinol | ND |
D-Pseudoephedrine |
>10000 | 4092 | 9125 | NDRA | Cathinol | [26] |
L-Pseudoephedrine | >10000 | 224 | 1988 | NRA | Cathinol | [26] |
Pseudophenmetrazine | >10000 | 514 | RI | NRA | Phenylmorpholine | [34] |
Psilocin | 561 | >10000 | >10000 | SRA | Tryptamine | [19] |
Serotonin | 44.4 | >10000 | >10000 | SRA | Tryptamine | [23] |
TFMPP |
121 | ND | >10000 | SRA | Arylpiperazine | [25] |
TFMCPP | 33 | >10000 | >10000 | SRA | Arylpiperazine | [19] |
Trimethoxyamphetamine |
16000 | >100000 | >100000 | IA | Amphetamine | [15] |
Tyramine | 2775 | 40.6 | 119 | NDRA | Phenethylamine | [23] |
The smaller the value, the more strongly the substance activates or releases the neurotransmitter. |
See also
References
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- ^ United States. Congress. Senate. Select Committee on Small Business. Subcommittee on Monopoly and Anticompetitive Activities (1976). Competitive problems in the drug industry: hearings before Subcommittee on Monopoly and Anticompetitive Activities of the Select Committee on Small Business, United States Senate, Ninetieth Congress, first session. U.S. Government Printing Office. pp. 2–.
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External links
- Media related to Monoamine releasing agents at Wikimedia Commons