3,4-Methylenedioxyamphetamine

Last updated

3,4-Methylenedioxyamphetamine
INN: Tenamfetamine
MDA-2D-skeletal.svg
MDA molecule ball.png
Clinical data
Other namesMDA; Tenamfetamine; Amphedoxamine; Sally; Sassafras; Sass-a-frass; Sass; Mellow Drug of America; Hug drug; Love; 3,4-Methylenedioxy-α-methylphenethylamine; 5-(2-Aminopropyl)-1,3-benzodioxole; EA-1298; NSC-9978; NSC-27106; SKF-5
Routes of
administration 		By mouth, sublingual, insufflation, intravenous
Drug class Serotonin–norepinephrine–dopamine releasing agent; Serotonin 5-HT2 receptor agonist; Entactogen; Empathogen; Serotonergic psychedelic; Hallucinogen; Stimulant
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Metabolism Hepatic (CYP extensively involved)
Elimination half-life 10.9 hours [2]
Duration of action 5–8 hours [3] [2]
Excretion Renal
Identifiers
  • 1-(2H-1,3-Benzodioxol-5-yl)propan-2-amine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.230.706 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C10H13NO2
Molar mass 179.219 g·mol−1
3D model (JSmol)
  • NC(C)CC1=CC2=C(C=C1)OCO2
  • InChI=1S/C10H13NO2/c1-7(11)4-8-2-3-9-10(5-8)13-6-12-9/h2-3,5,7H,4,6,11H2,1H3 Yes check.svgY
  • Key:NGBBVGZWCFBOGO-UHFFFAOYSA-N Yes check.svgY
   (verify)

3,4-Methylenedioxyamphetamine (MDA) is an entactogen, stimulant, and psychedelic drug of the amphetamine and MDxx families that is encountered mainly as a recreational drug. [3] [4] [5] It is usually taken orally. [3] [5]

Contents

In terms of its pharmacology, MDA is a serotonin–norepinephrine–dopamine releasing agent (SNDRA) and a serotonin 5-HT2 receptor agonist, including of the serotonin 5-HT2A receptor. [3] It has a duration of 5 to 8 hours. [3] [2]

MDA has a long history of psychotherapeutic and recreational use that predates that of MDMA, dating back to at least the mid-1960s. [3] [6] [4] It has been described as the first entactogen. [2] MDA has also been described as probably the most popular analogue of MDMA. [6] In most countries, the drug is a controlled substance and its possession and sale are illegal.

Use and effects

MDA is bought, sold, and used as a recreational drug due to its enhancement of mood and empathy. [7] It produces MDMA-like effects, including entactogenic and stimulant effects, as well as mild psychedelic effects. [2] [8] [9]

The dose range of MDA given in Alexander Shulgin's book PiHKAL (Phenethylamines I Have Known and Loved) and other sources is 80 to 160 mg. [5] [3] A wider recreational dose range for MDA of 20 to 200 mg or more, with a typical dose estimate of 90 mg, has also been reported. [10] The dose range of MDA is very similar to that of MDMA. [5] [3] [10] [2]

The effects of MDA include euphoria, empathy, emotional amplification, relaxation, feeling at peace with the world, increased introspection, self-awareness, and acceptance, authenticity, clarity of thought, a desire to communicate with others and relate personal issues, and emotional bonding with others. [3] [11] [12] These effects led to MDA being called the "love drug" or "hug drug". [11] [5] MDA also produces mild psychedelic effects, including brightened colors, closed-eye visuals or complex mental imagery, synaesthesia, and rarely mild hallucinations. [3] [2] It does not produce profound sensory disruption or overt hallucinations. [11] [12] In any case, the drug has still been found to produce mystical or spiritual experiences. [8] [2]

MDA shares most of MDMA's qualitative and emotional effects, including entactogenic and stimulant effects. [3] [12] [2] However, it has been said to be slightly less stimulating than MDMA. [3] [2] In addition, MDA's hallucinogenic effects are much greater than those of MDMA, although still less than those of classical psychedelics like psilocybin. [3] [11] [2] Another difference between the two drugs is that MDA appears to produce a more introverted and emotionally intense prosocial state, while MDMA encourages a more extroverted and gregarious prosocial state. [2]

Besides its psychoactive effects, MDA produces sympathomimetic effects such as increased heart rate and blood pressure, among other physiological effects. [6] [12] [2]

In terms of the individual enantiomers of MDA, (R)-MDA produces psychedelic effects and some entactogenic effects, while (S)-MDA is non-hallucinogenic, produces similar entactogenic effects as the racemate, and has considerable stimulant effects. [11] [12] [5] High doses of enantiopure (R)-MDA, in the range of 120 to 200 mg, are described as closely resembling the effects of LSD, for instance doses of 200 to 400 μg. [12] [13] Enantiopure (R)-MDA at high doses produces more robust psychedelic effects than typical doses of racemic MDA. [12] [13] [5]

The duration of MDA is about 5 to 8 hours and is about 2 hours longer than that of MDMA (3–6 hours). [3] [2] Shulgin originally gave a duration of MDA of 8 to 12 hours in PiHKAL, but he later revised this down to only 3 to 6 hours. [5] A modern clinical study gave a duration of 6 to 8 hours. [2]

Side effects

Side effects of MDA include sympathomimetic effects like increased heart rate and blood pressure as well as increased cortisol and prolactin levels. [2] [9]

Overdose

Symptoms of acute toxicity may include agitation, sweating, increased blood pressure and heart rate, dramatic increase in body temperature, convulsions, and death. Death is usually caused by cardiac effects and subsequent hemorrhaging in the brain (stroke). [14] [ medical citation needed ]

Interactions

Pharmacology

Pharmacodynamics

Activities of MDA
Target Affinity (Ki, nM)
SERT Tooltip Serotonin transporter5,600–>10,000 (Ki)
478–4,900 (IC50 Tooltip half-maximal inhibitory concentration)
160–162 (EC50 Tooltip Half-maximal effective concentration) (rat)
NET Tooltip Norepinephrine transporter13,000 (Ki)
150–420 (IC50)
47–108 (EC50) (rat)
DAT Tooltip Dopamine transporter>26,000 (Ki)
890–20,500 (IC50)
106–190 (EC50) (rat)
5-HT1A 3,762–>10,000
5-HT1B >10,000
5-HT1D >10,000
5-HT1E >10,000
5-HT1F ND
5-HT2A 3,200–>10,000 (Ki)
630–1,767 (EC50)
57–99% (Emax Tooltip maximal efficacy)
5-HT2B 91–100 (Ki)
190–850 (EC50)
51–80% (Emax)
5-HT2C 3,000–6,418 (Ki)
98–4,800 (EC50)
79–118% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A >10,000
5-HT6 >10,000
5-HT7 3,548
α1A 8,700–>10,000
α1B >10,000
α1D ND
α2A 1,100–2,600
α2B 690
α2C 229
β1, β2 >10,000
D1–D5 >10,000–>20,000
H1–H4 >10,000–>13,000
M1–M5 ND
nACh ND
TAAR1 220–250 (Ki) (rat)
740 (EC50) (rat)
86% (Emax) (rat)
160–180 (Ki) (mouse)
580 (EC50) (mouse)
102% (Emax) (rat)
3,600 (EC50) (human)
11% (Emax) (human)
I1 >10,000
σ1, σ2 ND
Notes: The smaller the value, the more avidly the drug binds to the site. Proteins are human unless otherwise specified. Refs: [15] [16] [17] [18] [19] [20] [21]
[22] [23] [24] [25]

MDA is a substrate of the serotonin, norepinephrine, dopamine, and vesicular monoamine transporters, and in relation to this, acts as a reuptake inhibitor and releasing agent of serotonin, norepinephrine, and dopamine (that is, it is an SNDRA Tooltip serotonin–norepinephrine–dopamine releasing agent). [3] [26] It is also an agonist of the serotonin 5-HT2A, [27] 5-HT2B, [28] and 5-HT2C receptors [29] and shows affinity for the α2A-, α2B-, and α2C-adrenergic receptors and serotonin 5-HT1A and 5-HT7 receptors. [30]

In addition to its actions as a monoamine releasing agent, MDA is a potent high-efficacy partial agonist or full agonist of the rodent TAAR1. [24] [25] Conversely, MDA is much weaker in terms of potency as an agonist of the human TAAR1. [24] [25] [31] Moreover, MDA acts as a very weak partial agonist or antagonist of the human TAAR1 rather than as an efficacious agonist. [24] [25] TAAR1 activation is thought to auto-inhibit and constrain the effects of amphetamines that act as TAAR1 agonists, for instance MDMA in rodents. [32] [33] [34] [35]

MDA fully substitutes for MDMA in rodent drug discrimination tests. [3] However, its prosocial effects in rodents are said to not fully resemble those of MDMA. [6] [36] MDA also substitutes for stimulants like dextroamphetamine and cocaine in drug discrimination tests. [3] [6] [11] The (S)-optical isomer of MDA is more potent than the (R)-optical isomer as a psychostimulant, possessing greater activity at the monoamine transporters. [3] [11] MDA and (R)-MDA but not (S)-MDA fully substitute for serotonergic psychedelics including DOM, LSD, and mescaline. [3] [37] [6] Similarly, MDA and (R)-MDA produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. [37] However, the head-twitch response they produce is very weak in magnitude compared to other related psychedelics such as the DOx drugs. [37] On the other hand, the response is more similar in magnitude to that of Ariadne. [37]

In terms of the subjective and behavioral effects of MDA, it is thought that serotonin release is required for its entactogenic effects, dopamine release is required for its euphoriant (rewarding and addictive) effects, dopamine and norepinephrine release are required for its psychostimulant effects, and direct agonism of the serotonin 5-HT2A receptor is required for its mild psychedelic effects. [3] The entactogenic effects of drugs like MDA are thought to dependent on a precise balance of serotonin and dopamine release as well as serotonin receptor agonism. [38] [39] [40] [41] [2] The longer duration of MDA compared to MDMA appears to be related to pharmacodynamics as opposed to pharmacokinetics, for instance the effects of MDA depending relatively more on serotonin 5-HT2A receptor agonism than on serotonin release. [2]

MDA can produce serotonergic neurotoxic effects in rodents. [3] [42] [43] This might in part be due to metabolism of MDA. [44] In addition, MDA activates a response of the neuroglia, though this subsides after use. [42]

Activities of MDMA, its enantiomers, and related compounds
Compound Monoamine release (EC50 Tooltip half-maximal effective concentration, nM)
Serotonin Norepinephrine Dopamine
Amphetamine NDNDND
   (S)-Amphetamine (d)698–1,7656.6–7.25.8–24.8
   (R)-Amphetamine (l)ND9.527.7
Methamphetamine NDNDND
   (S)-Methamphetamine (d)736–1,29212.3–13.88.5–24.5
   (R)-Methamphetamine (l)4,64028.5416
MDA160108190
  (S)-MDA (d)1005098
  (R)-MDA (l)310290900
MDMA 49.6–7254.1–11051.2–278
  (S)-MDMA (d)74136142
  (R)-MDMA (l)3405603,700
MDEA 472,608622
MBDB 5403,300>100,000
MDAI 1141171,334
Notes: The smaller the value, the more strongly the compound produces the effect. Refs: [45] [21] [46] [47] [48] [49] [50] [22]
MDA, MDMA, and enantiomers at serotonin 5-HT2 receptors
Compound 5-HT2A 5-HT2B 5-HT2C
EC50 (nM) Emax EC50 (nM) Emax EC50 (nM) Emax
Serotonin 5392%1.0100%2291%
MDA1,70057%19080%NDND
  (S)-MDA (d)18,20089%10081%7,40073%
  (R)-MDA (l)5,60095%15076%7,40076%
MDMA 6,10055%2,000–>20,00032%NDND
  (S)-MDMA (d)10,3009%6,00038%2,60053%
   (R)-MDMA (l)3,10021%90027%5,40027%
Notes: The smaller the Kact or EC50 value, the more strongly the compound produces the effect. Refs: [51] [21] [19]

Pharmacokinetics

The pharmacokinetics of MDA have been studied. [2] [52] Its duration of action has been reported to be about 6 to 8 hours. [8] The duration of MDA is longer than that of MDMA, about 8 hours for MDA versus 6 hours for MDMA. [2] [52] The elimination half-life of MDA is 10.9 hours. [2] Differences in the duration of MDA versus MDMA may be due pharmacodynamics rather than pharmacokinetics. [2] [52]

Chemistry

MDA is a substituted methylenedioxylated phenethylamine and amphetamine derivative. In relation to other phenethylamines and amphetamines, it is the 3,4-methylenedioxy, α-methyl derivative of β-phenylethylamine, the 3,4-methylenedioxy derivative of amphetamine, and the N-desmethyl derivative of MDMA.

It is a common adulterant of illicitly produced MDMA. [53] [54]

Synonyms

In addition to 3,4-methylenedioxyamphetamine, MDA is also known by other chemical synonyms such as the following:

Synthesis

MDA is typically synthesized from essential oils such as safrole or piperonal. Common approaches from these precursors include:

MDA analogs from safrole.png

Detection in body fluids

MDA may be quantitated in blood, plasma or urine to monitor for use, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Some drug abuse screening programs rely on hair, saliva, or sweat as specimens. Most commercial amphetamine immunoassay screening tests cross-react significantly with MDA and major metabolites of MDMA, but chromatographic techniques can easily distinguish and separately measure each of these substances. The concentrations of MDA in the blood or urine of a person who has taken only MDMA are, in general, less than 10% those of the parent drug. [64] [65] [66]

Derivatives and analogues

Analogues of MDA include its positional isomer 2,3-methylenedioxyamphetamine (2,3-MDA) and others.

MDA constitutes part of the core structure of the β-adrenergic receptor agonist protokylol.

History

MDA was first synthesized by Carl Mannich and W. Jacobsohn in 1910. [58] It was first taken in July 1930 by Gordon Alles at a total dose of 126 mg, who experienced hallucinogenic effects, well-being and euphoria, and peripheral effects. [67] [68] [69] However, he did not subsequently describe these effects until 1959. [70] [67] [68] Alles later licensed the drug to Smith, Kline & French. [69] MDA was first used in animal tests in 1939, and human trials began in 1941 in the exploration of possible therapies for Parkinson's disease. [12] However, it was found to be detrimental in people with Parkinson's disease. [12] The drug was described as having analeptic (psychostimulant) effects in humans in 1953. [12] From 1949 to 1957, more than five hundred human subjects were given MDA in an investigation of its potential use as an antidepressant or appetite suppressant by Smith, Kline & French. [12]

The United States Army also experimented with the drug, code named EA-1298, while working to develop a truth drug or incapacitating agent. Harold Blauer died in January 1953 after being intravenously injected, without his knowledge or consent, with 450 mg of the drug as part of Project MKUltra. [71] MDA was patented as an ataractic by Smith, Kline & French in 1960, and as an anorectic under the trade name "Amphedoxamine" in 1961. MDA began to appear on the recreational drug scene around 1963 to 1964. It was then inexpensive and readily available as a research chemical from several scientific supply houses. Several researchers, including Claudio Naranjo and Richard Yensen, have explored MDA in the field of psychotherapy. [72] [73]

The International Nonproprietary Name (INN) tenamfetamine was recommended by the World Health Organization (WHO) in 1986. [74] It was recommended in the same published list in which the INN of 2,5-dimethoxy-4-bromoamphetamine (DOB), brolamfetamine, was recommended. [74] These events suggest that MDA and DOB were under development as potential pharmaceutical drugs at the time. [74] The Multidisciplinary Association for Psychedelic Studies (MAPS) was also founded in 1986. [75]

Matthew J. Baggott and colleagues conducted some of the first modern clinical studies of MDA in humans and published their findings in the 2010s. [2] [8] [9]

Society and culture

MDA as prepared for recreational use. MDA.jpg
MDA as prepared for recreational use.

Names

When MDA was under development as a potential pharmaceutical drug, it was given the International Nonproprietary Name (INN) of tenamfetamine. [76]

Australia

MDA is schedule 9 prohibited substance under the Poisons Standards. [77] A schedule 9 substance is listed as a "Substances which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities." [77]

United States

MDA is a Schedule I controlled substance in the US.

Research

MDA has been studied in entactogen-assisted psychotherapy. [3] [6]

See also

References

  1. ↑ "RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control]. Brazilian Health Regulatory Agency (in Brazilian Portuguese). Diário Oficial da União (published 25 July 2023). 24 July 2023. Archived from the original on 27 August 2023. Retrieved 27 August 2023.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Baggott MJ, Garrison KJ, Coyle JR, Galloway GP, Barnes AJ, Huestis MA, Mendelson JE (15 March 2019). "Effects of the Psychedelic Amphetamine MDA (3,4-Methylenedioxyamphetamine) in Healthy Volunteers". Journal of Psychoactive Drugs. 51 (2): 108–117. doi:10.1080/02791072.2019.1593560. PMID   30967099. S2CID   106410946.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Oeri HE (May 2021). "Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy". J Psychopharmacol. 35 (5): 512–536. doi:10.1177/0269881120920420. PMC   8155739 . PMID   32909493.
  4. 1 2 Kaur H, Karabulut S, Gauld JW, Fagot SA, Holloway KN, Shaw HE, Fantegrossi WE (September 2023). "Balancing Therapeutic Efficacy and Safety of MDMA and Novel MDXX Analogues as Novel Treatments for Autism Spectrum Disorder". Psychedelic Medicine. 1 (3): 166–185. doi:10.1089/psymed.2023.0023. PMC   11661495 . PMID   40046567.
  5. 1 2 3 4 5 6 7 8 9 Alexander T. Shulgin, Ann Shulgin (1991). "#100 MDA 3,4-METHYLENEDIOXYAMPHETAMINE". PiHKAL: A Chemical Love Story (1st ed.). Berkeley, CA: Transform Press. pp. 714–719. ISBN   978-0-9630096-0-9. OCLC   25627628.
  6. 1 2 3 4 5 6 7 Sáez-Briones P, Hernández A (September 2013). "MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology". Curr Neuropharmacol. 11 (5): 521–534. doi:10.2174/1570159X11311050007. PMC   3763760 . PMID   24403876.
  7. ↑ Monte AP, Marona-Lewicka D, Cozzi NV, Nichols DE (November 1993). "Synthesis and pharmacological examination of benzofuran, indan, and tetralin analogues of 3,4-(methylenedioxy)amphetamine". Journal of Medicinal Chemistry. 36 (23): 3700–3706. doi:10.1021/jm00075a027. PMID   8246240.
  8. 1 2 3 4 Baggott MJ, Siegrist JD, Galloway GP, Robertson LC, Coyle JR, Mendelson JE (December 2010). "Investigating the mechanisms of hallucinogen-induced visions using 3,4-methylenedioxyamphetamine (MDA): a randomized controlled trial in humans". PLOS ONE. 5 (12) e14074. Bibcode:2010PLoSO...514074B. doi: 10.1371/journal.pone.0014074 . PMC   2996283 . PMID   21152030.
  9. 1 2 3 Baggott MJ, Siegrist J, Coyle JR, Flower K, Galloway G, Mendelson J (2010). "Poster Session III (PIII 1-84): PIII-09 Pharmacodynamic Effects of 3,4-Methylenedioxyamphetamine (MDA)". Clinical Pharmacology & Therapeutics. 87 (Suppl 1): S68–S95 (S70). doi:10.1038/clpt.2009.277. ISSN   0009-9236. In a placebo-controlled, double-blind, within-subjects study, 12 individuals received a single 98 mg/70 kg bw dose of MDA. This is the molar equivalent of 105 mg/ 70 kg bw MDMA, a well-studied dose. [...] MDA increased cortisol by 16.39 ug/dL (95%CI: 13.03-19.74, P < 1e-3) and prolactin by 18.37 ng/mL (95%CI: 7.39-29.35, P < 1e-3). These hormonal changes are comparable to those seen after MDMA. Heart rate increased by 9.05 bpm (95%CI: 6.10-11.99, P < 1e-5) and blood pressure increased by 18.98 / 12.73 mm Hg (Systolic 95%CI: 16.47 - 21.49, P < 1e-7; Diastolic 95%CI: 10.82 - 14.63, P < 1e-4). [...] There were robust self-report VAS changes in both MDMA-like (e.g., "closeness to others") and hallucinogen-like (e.g., "familiar things seem unfamiliar", time distortions, closed-eye visuals) effects that were generally similar to those seen after MDMA. [...] MDA is a psychoactive sympathomimetic phenethylamine with effects similar to MDMA. Although differences may exist in the magnitude of physiological effects, the overall profiles appear remarkably similar.
  10. 1 2 Luethi D, Liechti ME (October 2018). "Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics". Int J Neuropsychopharmacol. 21 (10): 926–931. doi:10.1093/ijnp/pyy047. PMC   6165951 . PMID   29850881. Supplementary Table S1. Dose estimates and data sources for stimulants. [...]
  11. 1 2 3 4 5 6 7 Nichols DE (1986). "Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens". J Psychoactive Drugs. 18 (4): 305–313. doi:10.1080/02791072.1986.10472362. PMID   2880944.
  12. 1 2 3 4 5 6 7 8 9 10 11 Shulgin AT (1978). "Psychotomimetic Drugs: Structure-Activity Relationships". In Iversen LL, Iversen SD, Snyder SH (eds.). Stimulants. Boston, MA: Springer US. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN   978-1-4757-0512-6.
  13. 1 2 Yensen R, Di Leo FB, Rhead JC, Richards WA, Soskin RA, Turek B, Kurland AA (October 1976). "MDA-assisted psychotherapy with neurotic outpatients: a pilot study". J Nerv Ment Dis. 163 (4): 233–245. doi:10.1097/00005053-197610000-00002. PMID   972325.
  14. ↑ Diaz J (1996). How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall.
  15. ↑ "PDSP Database". UNC (in Zulu). Retrieved 13 December 2024.
  16. ↑ Liu T. "BindingDB BDBM50005247 (+/-)2-Benzo[1,3]dioxol-5-yl-1-methyl-ethylamine::(-)2-Benzo[1,3]dioxol-5-yl-1-methyl-ethylamine::(R)-(-)-2-Benzo[1,3]dioxol-5-yl-1-methyl-ethylamine::(S)-(+)-2-Benzo[1,3]dioxol-5-yl-1-methyl-ethylamine::2-Benzo[1,3]dioxol-5-yl-1-methyl-ethylamine::2-Benzo[1,3]dioxol-5-yl-1-methyl-ethylamine((R)-(-)-MDA)::3,4-methylenedioxyamphetamine::CHEMBL6731::MDA::MDA, (R,S)::MDA,R(-)::Tenamfetamine::methylenedioxyamphetamine". BindingDB. Retrieved 13 December 2024.
  17. ↑ Ray TS (February 2010). "Psychedelics and the human receptorome". PLOS ONE. 5 (2) e9019. Bibcode:2010PLoSO...5.9019R. doi: 10.1371/journal.pone.0009019 . PMC   2814854 . PMID   20126400.
  18. ↑ Luethi D, Kolaczynska KE, Walter M, Suzuki M, Rice KC, Blough BE, Hoener MC, Baumann MH, Liechti ME (July 2019). "Metabolites of the ring-substituted stimulants MDMA, methylone and MDPV differentially affect human monoaminergic systems". J Psychopharmacol. 33 (7): 831–841. doi:10.1177/0269881119844185. PMC   8269116 . PMID   31038382.
  19. 1 2 Kolaczynska KE, Ducret P, Trachsel D, Hoener MC, Liechti ME, Luethi D (June 2022). "Pharmacological characterization of 3,4-methylenedioxyamphetamine (MDA) analogs and two amphetamine-based compounds: N,α-DEPEA and DPIA". Eur Neuropsychopharmacol. 59: 9–22. doi: 10.1016/j.euroneuro.2022.03.006 . PMID   35378384.
  20. ↑ Rickli A, Kopf S, Hoener MC, Liechti ME (July 2015). "Pharmacological profile of novel psychoactive benzofurans". Br J Pharmacol. 172 (13): 3412–3425. doi:10.1111/bph.13128. PMC   4500375 . PMID   25765500.
  21. 1 2 3 Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I, Glennon RA, Blough B, Rothman RB, Roth BL (June 2003). "3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro". Mol Pharmacol. 63 (6): 1223–1229. doi:10.1124/mol.63.6.1223. PMID   12761331.
  22. 1 2 Blough B (July 2008). "Dopamine-releasing agents" (PDF). In Trudell ML, Izenwasser S (eds.). Dopamine Transporters: Chemistry, Biology and Pharmacology. Hoboken [NJ]: Wiley. pp. 305–320. ISBN   978-0-470-11790-3. OCLC   181862653. OL   18589888W.
  23. ↑ Brandt SD, Walters HM, Partilla JS, Blough BE, Kavanagh PV, Baumann MH (December 2020). "The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats". Psychopharmacology (Berl). 237 (12): 3703–3714. doi:10.1007/s00213-020-05648-z. PMC   7686291 . PMID   32875347.
  24. 1 2 3 4 Gainetdinov RR, Hoener MC, Berry MD (July 2018). "Trace Amines and Their Receptors". Pharmacol Rev. 70 (3): 549–620. doi: 10.1124/pr.117.015305 . PMID   29941461.
  25. 1 2 3 4 Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME (April 2016). "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1" (PDF). J Pharmacol Exp Ther. 357 (1): 134–144. doi:10.1124/jpet.115.229765. PMID   26791601. Archived from the original (PDF) on 9 May 2025.
  26. ↑ Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry. 6 (17): 1845–1859. doi:10.2174/156802606778249766. PMID   17017961.
  27. ↑ Di Giovanni G, Di Matteo V, Esposito E (2008). Serotonin–dopamine Interaction: Experimental Evidence and Therapeutic Relevance. Elsevier. pp. 294–. ISBN   978-0-444-53235-0.
  28. ↑ Rothman RB, Baumann MH (May 2009). "Serotonergic drugs and valvular heart disease". Expert Opinion on Drug Safety. 8 (3): 317–329. doi:10.1517/14740330902931524. PMC   2695569 . PMID   19505264.
  29. ↑ Nash JF, Roth BL, Brodkin JD, Nichols DE, Gudelsky GA (August 1994). "Effect of the R(−) and S(+) isomers of MDA and MDMA on phosphatidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors". Neuroscience Letters. 177 (1–2): 111–115. doi:10.1016/0304-3940(94)90057-4. PMID   7824160. S2CID   41352480.
  30. ↑ Ray TS (February 2010). "Psychedelics and the human receptorome". PLOS ONE. 5 (2) e9019. Bibcode:2010PLoSO...5.9019R. doi: 10.1371/journal.pone.0009019 . PMC   2814854 . PMID   20126400.
  31. ↑ Lewin AH, Miller GM, Gilmour B (December 2011). "Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class". Bioorganic & Medicinal Chemistry. 19 (23): 7044–7048. doi:10.1016/j.bmc.2011.10.007. PMC   3236098 . PMID   22037049.
  32. ↑ Espinoza S, Gainetdinov RR (2014). "Neuronal Functions and Emerging Pharmacology of TAAR1". Taste and Smell. Topics in Medicinal Chemistry. Vol. 23. Cham: Springer International Publishing. pp. 175–194. doi:10.1007/7355_2014_78. ISBN   978-3-319-48925-4. Interestingly, the concentrations of amphetamine found to be necessary to activate TAAR1 are in line with what was found in drug abusers [3, 51, 52]. Thus, it is likely that some of the effects produced by amphetamines could be mediated by TAAR1. Indeed, in a study in mice, MDMA effects were found to be mediated in part by TAAR1, in a sense that MDMA auto-inhibits its neurochemical and functional actions [46]. Based on this and other studies (see other section), it has been suggested that TAAR1 could play a role in reward mechanisms and that amphetamine activity on TAAR1 counteracts their known behavioral and neurochemical effects mediated via dopamine neurotransmission.
  33. ↑ Kuropka P, Zawadzki M, Szpot P (May 2023). "A narrative review of the neuropharmacology of synthetic cathinones-Popular alternatives to classical drugs of abuse". Hum Psychopharmacol. 38 (3) e2866. doi:10.1002/hup.2866. PMID   36866677. Another feature that distinguishes [synthetic cathinones (SCs)] from amphetamines is their negligible interaction with the trace amine associated receptor 1 (TAAR1). Activation of this receptor reduces the activity of dopaminergic neurones, thereby reducing psychostimulatory effects and addictive potential (Miller, 2011; Simmler et al., 2016). Amphetamines are potent agonists of this receptor, making them likely to self‐inhibit their stimulating effects. In contrast, SCs show negligible activity towards TAAR1 (Kolaczynska et al., 2021; Rickli et al., 2015; Simmler et al., 2014, 2016). [...] It is worth noting, however, that for TAAR1 there is considerable species variability in its interaction with ligands, and it is possible that the in vitro activity of [rodent TAAR1 agonists] may not translate into activity in the human body (Simmler et al., 2016). The lack of self‐regulation by TAAR1 may partly explain the higher addictive potential of SCs compared to amphetamines (Miller, 2011; Simmler et al., 2013).
  34. ↑ Simmler LD, Buser TA, Donzelli M, Schramm Y, Dieu LH, Huwyler J, Chaboz S, Hoener MC, Liechti ME (January 2013). "Pharmacological characterization of designer cathinones in vitro". Br J Pharmacol. 168 (2): 458–470. doi:10.1111/j.1476-5381.2012.02145.x. PMC   3572571 . PMID   22897747. β-Keto-analogue cathinones also exhibited approximately 10-fold lower affinity for the TA1 receptor compared with their respective non-β-keto amphetamines. [...] Activation of TA1 receptors negatively modulates dopaminergic neurotransmission. Importantly, methamphetamine decreased DAT surface expression via a TA1 receptor-mediated mechanism and thereby reduced the presence of its own pharmacological target (Xie and Miller, 2009). MDMA and amphetamine have been shown to produce enhanced DA and 5-HT release and locomotor activity in TA1 receptor knockout mice compared with wild-type mice (Lindemann et al., 2008; Di Cara et al., 2011). Because methamphetamine and MDMA auto-inhibit their neurochemical and functional effects via TA1 receptors, low affinity for these receptors may result in stronger effects on monoamine systems by cathinones compared with the classic amphetamines.
  35. ↑ Di Cara B, Maggio R, Aloisi G, Rivet JM, Lundius EG, Yoshitake T, Svenningsson P, Brocco M, Gobert A, De Groote L, Cistarelli L, Veiga S, De Montrion C, Rodriguez M, Galizzi JP, Lockhart BP, Cogé F, Boutin JA, Vayer P, Verdouw PM, Groenink L, Millan MJ (November 2011). "Genetic deletion of trace amine 1 receptors reveals their role in auto-inhibiting the actions of ecstasy (MDMA)". J Neurosci. 31 (47): 16928–16940. doi:10.1523/JNEUROSCI.2502-11.2011. PMC   6623861 . PMID   22114263.
  36. ↑ Sáez-Briones P, Castro V, Maass M, Mundaca E, Villagra M, Díaz-Véliz G. Modelo animal de interacción social: administración aguda de MDMA (3-4-metilendioximetanfetamina “Extasis”) y algunos de sus análogos en ratas Sprague-Dawley. Rev. Farmacol. Chile. 2011;4: 72.
  37. 1 2 3 4 Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD (May 2020). "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species" (PDF). Neuropharmacology. 167 107933. doi:10.1016/j.neuropharm.2019.107933. PMC   9191653 . PMID   31917152.
  38. ↑ Luethi D, Liechti ME (April 2020). "Designer drugs: mechanism of action and adverse effects". Arch Toxicol. 94 (4): 1085–1133. Bibcode:2020ArTox..94.1085L. doi:10.1007/s00204-020-02693-7. PMC   7225206 . PMID   32249347.
  39. ↑ Baggott M (23 June 2023). Beyond Ecstasy: Progress in Developing and Understanding a Novel Class of Therapeutic Medicine. PS2023 [Psychedelic Science 2023, June 19–23, 2023, Denver, Colorado]. Denver, CO: Multidisciplinary Association for Psychedelic Studies.
  40. ↑ "Better Than Ecstasy: Progress in Developing a Novel Class of Therapeutic with Matthew Baggott, PhD". YouTube. 6 March 2024. Retrieved 20 November 2024.
  41. ↑ Rothman RB, Baumann MH (July 2002). "Therapeutic and adverse actions of serotonin transporter substrates". Pharmacol Ther. 95 (1): 73–88. doi:10.1016/s0163-7258(02)00234-6. PMID   12163129.
  42. 1 2 Herndon JM, Cholanians AB, Lau SS, Monks TJ (March 2014). "Glial cell response to 3,4-(+/-)-methylenedioxymethamphetamine and its metabolites". Toxicological Sciences. 138 (1): 130–138. doi:10.1093/toxsci/kft275. PMC   3930364 . PMID   24299738.
  43. ↑ Kalant H (October 2001). "The pharmacology and toxicology of "ecstasy" (MDMA) and related drugs". CMAJ. 165 (7): 917–928. PMC   81503 . PMID   11599334.
  44. ↑ de la Torre R, Farré M, Roset PN, Pizarro N, Abanades S, Segura M, et al. (April 2004). "Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition". Therapeutic Drug Monitoring. 26 (2): 137–144. doi:10.1097/00007691-200404000-00009. PMID   15228154.
  45. ↑ Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry. 6 (17): 1845–1859. doi:10.2174/156802606778249766. PMID   17017961.
  46. ↑ Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS (January 2001). "Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin". Synapse. 39 (1): 32–41. doi:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3. PMID   11071707. S2CID   15573624.
  47. ↑ Rothman RB, Partilla JS, Baumann MH, Lightfoot-Siordia C, Blough BE (April 2012). "Studies of the biogenic amine transporters. 14. Identification of low-efficacy "partial" substrates for the biogenic amine transporters". The Journal of Pharmacology and Experimental Therapeutics. 341 (1): 251–262. doi:10.1124/jpet.111.188946. PMC   3364510 . PMID   22271821.
  48. ↑ Marusich JA, Antonazzo KR, Blough BE, Brandt SD, Kavanagh PV, Partilla JS, Baumann MH (February 2016). "The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue". Neuropharmacology. 101: 68–75. doi:10.1016/j.neuropharm.2015.09.004. PMC   4681602 . PMID   26362361.
  49. ↑ Nagai F, Nonaka R, Satoh Hisashi Kamimura K (March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology. 559 (2–3): 132–137. doi:10.1016/j.ejphar.2006.11.075. PMID   17223101.
  50. ↑ Halberstadt AL, Brandt SD, Walther D, Baumann MH (March 2019). "2-Aminoindan and its ring-substituted derivatives interact with plasma membrane monoamine transporters and α2-adrenergic receptors". Psychopharmacology (Berl). 236 (3): 989–999. doi:10.1007/s00213-019-05207-1. PMC   6848746 . PMID   30904940.
  51. ↑ Nash JF, Roth BL, Brodkin JD, Nichols DE, Gudelsky GA (August 1994). "Effect of the R(-) and S(+) isomers of MDA and MDMA on phosphatidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors". Neurosci Lett. 177 (1–2): 111–115. doi:10.1016/0304-3940(94)90057-4. PMID   7824160.
  52. 1 2 3 Baggott MJ, Li L, Galloway GP, Scheidweiler KB, Barnes AJ, Huestis MA, Mendelson J (2012). "Poster Session III (PIII 1-110): PIII-110: Pharmacokinetics of Oral 3,4-Methylenedioxyamphetamine in Humans". Clinical Pharmacology & Therapeutics. 91 (Suppl 1): S96 –S135. doi:10.1038/clpt.2011.363. ISSN   0009-9236. Knowledge of MDA and HMA kinetics in humans is limited to data from MDMA administration studies where minimal formation of these compounds likely leads to inaccurate parameter estimation. We administered a single [98 mg/70 kg body weight] oral dose of MDA to participants in a controlled setting to characterize plasma MDA pharmacokinetics for the first time. [...] Cmax and AUC0-∞ for MDA were 229 ± 39 ng/mL (mean ± SD) and 3636 ± 958 for MDA and 92 ± 61 ng/mL and 1544 ± 741 for the metabolite HMA. Total MDA clearance was 30267 ± 8214 mL/min. There was considerable between-subject variation in metabolite exposure: HMA Cmax and AUC varied over 7-fold and 4-fold, respectively, between the highest and lowest individuals. [...] Pharmacokinetics of MDA resemble those of an iso-molar dose of MDMA, suggesting differences in duration of acute effects between MDA and MDMA are not due to kinetic differences.
  53. ↑ "EcstasyData.org: Test Result Statistics: Substances by Year". EcstasyData.org. Retrieved 27 June 2017.
  54. ↑ "Trans European Drug Information". idpc.net. Archived from the original on 4 November 2021. Retrieved 27 June 2017.
  55. ↑ Muszynski E (1961). "[Production of some amphetamine derivatives]". Acta Poloniae Pharmaceutica. 18: 471–478. PMID   14477621.
  56. 1 2 3 Shulgin A, Manning T, Daley P (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds (1 ed.). Berkeley, CA: Transform Press. p. 165. ISBN   978-0-9630096-3-0.
  57. ↑ Noggle FT, DeRuiter J, Long MJ (1986). "Spectrophotometric and liquid chromatographic identification of 3,4-methylenedioxyphenylisopropylamine and its N-methyl and N-ethyl homologs". Journal of the Association of Official Analytical Chemists. 69 (4): 681–686. PMID   2875058.
  58. 1 2 Mannich C, Jacobsohn W, Mannich HC (1910). "Über Oxyphenyl-alkylamine und Dioxyphenyl-alkylamine". Berichte der Deutschen Chemischen Gesellschaft. 41 (1): 189–197. doi:10.1002/cber.19100430126.
  59. ↑ Ho BT, McIsaac WM, An R, Tansey LW, Walker KE, Englert LF, Noel MB (January 1970). "Analogs of alpha-methylphenethylamine (amphetamine). I. Synthesis and pharmacological activity of some methoxy and/or methyl analogs". Journal of Medicinal Chemistry. 13 (1): 26–30. doi:10.1021/jm00295a007. PMID   5412110.
  60. ↑ Butterick JR, Unrau AM (1974). "Reduction of β-nitrostyrene with sodium bis-(2-methoxyethoxy)-aluminium dihydride. A convenient route to substituted phenylisopropylamines". Journal of the Chemical Society, Chemical Communications. 8 (8): 307–308. doi:10.1039/C39740000307.
  61. ↑ Toshitaka O, Hiroaka A (1992). "Synthesis of Phenethylamine Derivatives as Hallucinogen". Japanese Journal of Toxicology and Environmental Health. 38 (6): 571–580. doi: 10.1248/jhs1956.38.571 . Retrieved 20 June 2014.
  62. ↑ Elks J, Hey DH (1943). "7. β-3 : 4-Methylenedioxyphenylisopropylamine". J. Chem. Soc.: 15–16. doi:10.1039/JR9430000015. ISSN   0368-1769.
  63. ↑ Victor C, D R (28 November 2021). "Does the 'Two Dogs' Method of Clandestine Synthesis Use Precursors That are not Legally Regulated on the Australian East Coast? by Victor Chiruta, Robert D Renshaw :: SSRN". SSRN   3973132 . Retrieved 11 February 2024.
  64. ↑ Kolbrich EA, Goodwin RS, Gorelick DA, Hayes RJ, Stein EA, Huestis MA. Plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine after controlled oral administration to young adults. Ther. Drug Monit. 30: 320–332, 2008.
  65. ↑ Barnes AJ, De Martinis BS, Gorelick DA, Goodwin RS, Kolbrich EA, Huestis MA (March 2009). "Disposition of MDMA and metabolites in human sweat following controlled MDMA administration". Clinical Chemistry. 55 (3): 454–462. doi:10.1373/clinchem.2008.117093. PMC   2669283 . PMID   19168553.
  66. ↑ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 9th edition, Biomedical Publications, Seal Beach, California, 2011, pp. 1078–1080.
  67. 1 2 Gordon A. Alles (1959). "Some Relations Between Chemical Structure and Physiological Action of Mescaline and Related Compounds / Structure and Action of Phenethylamines". In Abramson HA (ed.). Neuropharmacology: Transactions of the Fourth Conference, September 25, 26, and 27, 1957, Princeton, N. J. New York: Josiah Macy Foundation. pp. 181–268. OCLC   9802642. Archived from the original on 21 March 2025.
  68. 1 2 Gordon A. Alles (1959). "Subjective Reactions to Phenethylamine Hallucinogens". A Pharmacologic Approach to the Study of the Mind. Springfield: CC Thomas. pp. 238–250 (241–246). ISBN   978-0-398-04254-7.{{cite book}}: ISBN / Date incompatibility (help)
  69. 1 2 Matthew J. Baggott (18 July 2008). "The First MDA trip and the measurement of 'mystical experience' after MDA, LSD, and Psilocybin". Psychedelic Research. Archived from the original on 13 July 2012.
  70. ↑ Benzenhöfer U, Passie T (August 2010). "Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin". Addiction. 105 (8): 1355–61. doi:10.1111/j.1360-0443.2010.02948.x. PMID   20653618.
  71. ↑ Dunlap LE, Andrews AM, Olson DE (October 2018). "Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine" (PDF). ACS Chem Neurosci. 9 (10): 2408–2427. doi:10.1021/acschemneuro.8b00155. PMC   6197894 . PMID   30001118.
  72. ↑ Naranjo C, Shulgin AT, Sargent T (1967). "Evaluation of 3,4-methylenedioxyamphetamine (MDA) as an adjunct to psychotherapy". Medicina et Pharmacologia Experimentalis. International Journal of Experimental Medicine. 17 (4): 359–364. doi:10.1159/000137100. PMID   5631047.
  73. ↑ Yensen R, Di Leo FB, Rhead JC, Richards WA, Soskin RA, Turek B, Kurland AA (October 1976). "MDA-assisted psychotherapy with neurotic outpatients: a pilot study". The Journal of Nervous and Mental Disease. 163 (4): 233–245. doi:10.1097/00005053-197610000-00002. PMID   972325. S2CID   41155810.
  74. 1 2 3 "INN Recommended List 26". World Health Organization (WHO). 9 June 1986. Retrieved 3 November 2024.
  75. ↑ Emerson A, Ponté L, Jerome L, Doblin R (2014). "History and future of the Multidisciplinary Association for Psychedelic Studies (MAPS)". J Psychoactive Drugs. 46 (1): 27–36. doi:10.1080/02791072.2014.877321. PMID   24830183.
  76. ↑ Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 1157. ISBN   978-1-4757-2085-3 . Retrieved 13 November 2024.
  77. 1 2 Poisons Standard (October 2015) comlaw.gov.au
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