4-Methylthioamphetamine

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4-Methylthioamphetamine
Legal status
Legal status
Identifiers
  • 1-[4-(Methylsulfanyl)phenyl]propan-2-amine
JSmol)
  • NC(C)CC(C=C1)=CC=C1SC
  • InChI=1S/C10H15NS/c1-8(11)7-9-3-5-10(12-2)6-4-9/h3-6,8H,7,11H2,1-2H3 checkY
  • Key:OLEWMKVPSUCNLG-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

4-Methylthioamphetamine (4-MTA) is a

selective serotonin releasing agent (SSRA) in animals.[2][3][4] 4-MTA is the methylthio derivative of amphetamine
.

History

First appearance

In 1997, the

hydrochloride salt
form, and pictures of the different tablets were compared to each other. After an investigation, it appeared that in other European countries such as the United Kingdom and Germany the derivative was also encountered. The new drug even got as far as Australia. After analytical research, the compound was identified as 4-methylthioamphetamine (4-MTA). This was an already known compound originally only intended for pharmacological studies on animals. The studies of 4-MTA by David Nichols were then linked to the tablets found in all the different countries.

Development

Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. 4-MTA was ranked 12th in dependence, 10th in physical harm, and 17th in social harm.[6]

4-MTA was developed by the research team led by David Nichols

ecstasy, which was probably the motivation for its production and distribution to humans.[7] Nichols also said, "I have never considered my research to be dangerous, and in fact hoped one day to develop medicines to help people."[7]
Because of the 4-MTA relating death, Nichols' laboratory was asked to study the human effects of other materials they have studied, to avoid likewise situation as with 4-MTA. Most of the molecules the laboratory further had published could not kill in reasonable dosages.

Use and availability

The typical tablets sold on the street contained approximately between 100–140 mg 4-MTA.[8] 4-MTA was briefly sold in smart shops in the Netherlands, though was soon banned by the Dutch government after serious side-effects started to emerge. The Union of Smartshop Owners decided to leave it out of their assortment after they discovered the drug had only been tested on rats.[9] It was also briefly sold on the black market as MDMA during the late 1990s, mainly in the US, but proved unpopular due to its high risk of severe side effects (several deaths were reported) and relative lack of positive euphoria.[10]

Effects

4-MTA is a strong serotonin releaser similar to

better source needed] Therefore, the major neuropharmacological effect is an increased release of serotonin, and the inhibition of serotonin uptake of mono oxidase A (MAO-A). The combination of the releasing of serotonin from neurons, but the prevention of breaking this neurotransmitter down again, leads to dangerous serotonin syndrome
. The serotonin syndrome is a hyper serotonergic state, which can become fatal and is a side effect of serotonergic enhancing drugs. The symptoms of serotonin syndrome caused by 4-MTA are described in the Report on the Risk Assessment of 4-MTA

Symptoms of the serotonin syndrome caused by 4-MTA

  • Euphoria
  • Drowsiness
  • Sustained rapid eye movement
  • Hyperreflexia – overreaction of the reflexes
  • Agitation
  • Restlessness
  • Tachycardia – fast heart rate
  • Headache
  • Clumsiness
  • Disorientation
  • Intoxication – feeling drunk and dizzy
  • Rigidity
  • Rapid muscle contraction and relaxation in the ankle causing abnormal movements of the foot
  • Muscle contraction and relaxation in the jaw
  • Muscle twitching leading to hyperthermia
  • Shivering
  • High body temperature
  • Sweating
  • Altered mental status (including confusion and hypomania – a 'happy drunk state')

[15] Another effect is the increase of the secretion of several hormones, like adrenocorticotropic hormone (ACTH), corticosterone, prolactin, oxytocin, and renin induced by 4-MTA through stimulation of serotonergic neurotransmission.

There has been suggested that 4-MTA because of its slow onset of action, is more dangerous than other designer drugs. Users of the drug rapidly take another dose because they assume the first was inadequate; thus increasing the possibility of an overdose. (EMCDDA, 1999)

Today the knowledge about the effects of 4-MTA is narrow, because of very limited research and experimental data. The only 4 studies that are conducted show a weak effect on dopamine and noradrenaline. This study was executed with a single dose of 4-MTA, no study where the effect of multiple doses 4-MTA where researched exist up to date.[citation needed]

Chemistry

In a procedure analogous to the production of other amphetamines, 4-MTA has been prepared from 4-(methylthio)phenylacetone by the Leuckart reaction and the reaction byproducts have been characterized.[16]

Metabolism

How 4-MTA is metabolized by rats

4-MTA undergoes limited biotransformation, the metabolic pathways of the metabolites in humans is postulated in the following steps:

  1. β-Hydroxylation of the side chain to 4-hydroxy-4-methylthioamphetamine (step I).
  2. Ring hydroxylation to a phenolic structure (step II).
  3. Oxidative deamination to form an oxo metabolite, followed by (step III):
    • reduction into the corresponding alcohol (step IIIa),
    • degradation of the side chain to 4-methylthiobenzoic acid (step IIIb).[17]

The main metabolite was identified as 4-methylthiobenzoic acid. This compound leads to bioactivation (toxification), since the metabolite increases dramatically the sensitivity to the reduction in ATP content.[18] The biotransformation shows great similarities to the metabolic pathway of the structurally related 4-methoxyamphetamine [17]

See also

References

  1. ^ Anvisa (2023-07-24). "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] (in Brazilian Portuguese). Diário Oficial da União (published 2023-07-25). Archived from the original on 2023-08-27. Retrieved 2023-08-27.
  2. ^
    PMID 1473561
    .
  3. PMID 8968349
    .
  4. PMID 12191583
    .
  5. PMID 10423848
    .
  6. S2CID 5903121
    .
  7. ^
    PMID 21209630
    .
  8. PMID 19766415
    .
  9. ^ "Report on the Risk Assessment of 4-MTA in the Framework of the Joint Action on New Synthetic Drugs" (PDF). Joint Action on New Synthetic Drugs: 8. 1999-05-19. Archived (PDF) from the original on 2020-09-18. Retrieved 2022-08-21 – via European Monitoring Centre for Drugs and Drug Addiction.
  10. ^ "Ecstasy Or MDMA (also Known As Molly)". www.dea.gov. Archived from the original on 2022-08-21. Retrieved 2022-08-21.
  11. PMID 10732944. [verification needed
    ]
  12. S2CID 45796753. [verification needed
    ]
  13. PMID 11765028. [verification needed
    ]
  14. S2CID 40206693. [verification needed
    ]
  15. ^ "Report on the Rist Assessment of 4-MTA in the Framework of the Joint Action on New Synthetic Drugs" (PDF). 1999-05-19.
  16. PMID 21982394
    .
  17. ^
    PMID 16027051
    .
  18. S2CID 35836705
    .

External links
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