Misplaced Pages

para-Methoxyamphetamine

Clinical data
Trade names	Dr.Death
Routes of administration	Oral
ATC code	none
Legal status
Legal status	AU: S9 (Prohibited substance) BR: Class F2 (Prohibited psychotropics) CA: Schedule I DE: Anlage I (Authorized scientific use only) UK: Class A US: Schedule I UN: Psychotropic Schedule I In general illegal unless that was for medical, therapeutic or scientific use.
Identifiers
IUPAC name 1-(4-methoxyphenyl)propan-2-amine
CAS Number	64-13-1
PubChem CID	31721
DrugBank	DB01472
ChemSpider	29417
UNII	OVB8F8P39Q
KEGG	C22811
ChEMBL	ChEMBL278663
CompTox Dashboard (EPA)	DTXSID7040578
ECHA InfoCard	100.000.525
Chemical and physical data
Formula	C10H15NO
Molar mass	165.236 g·mol
3D model (JSmol)	Interactive image
SMILES C1=CC(=CC=C1CC(C)N)OC
InChI InChI=1S/C10H15NO/c1-8(11)7-9-3-5-10(12-2)6-4-9/h3-6,8H,7,11H2,1-2H3 Key:NEGYEDYHPHMHGK-UHFFFAOYSA-N
(what is this?)  (verify)

para-Methoxyamphetamine (PMA), also known as 4-methoxyamphetamine (4-MA), is a designer drug of the amphetamine class with serotonergic effects. Unlike other similar drugs of this family, PMA does not produce stimulant, euphoriant, or entactogen effects, and behaves more like an antidepressant in comparison, though it does have some psychedelic properties.

PMA has been found in tablets touted as MDMA (ecstasy) although its effects are markedly different compared to those of MDMA. The consequences of such deception have often included hospitalization and death for unwitting users. PMA is commonly synthesized from anethole, the flavor compound of anise and fennel, mainly because the starting material for MDMA, safrole, has become less available due to law enforcement action, causing illicit drug manufacturers to use anethole as an alternative.

Adverse effects

PMA has been associated with numerous adverse reactions including death. Effects of PMA ingestion include many effects of the hallucinogenic amphetamines including accelerated and irregular heartbeat, blurred vision, and a strong feeling of intoxication that is often unpleasant. At high doses unpleasant effects such as nausea and vomiting, severe hyperthermia and hallucinations may occur. The effects of PMA also seem to be much more unpredictable and variable between individuals than those of MDMA, and sensitive individuals may die from a dose of PMA by which a less susceptible person might only be mildly affected. While PMA alone may cause significant toxicity, the combination of PMA with MDMA has a synergistic effect that seems to be particularly hazardous. Since PMA has a slow onset of effects, several deaths have occurred where individuals have taken a pill containing PMA, followed by a pill containing MDMA some time afterwards due to thinking that the first pill was not active.

Overdose

PMA overdose can be a serious medical emergency that may occur at only slightly above the usual recreational dose range, especially if PMA is mixed with other stimulant drugs such as cocaine or MDMA. Characteristic symptoms are pronounced hyperthermia, tachycardia, and hypertension, along with agitation, confusion, and convulsions. PMA overdose also tends to cause hypoglycaemia and hyperkalaemia, which can help to distinguish it from MDMA overdose. Complications can sometimes include more serious symptoms such as rhabdomyolysis and cerebral hemorrhage, requiring emergency surgery. There is no specific antidote, so treatment is symptomatic, and usually includes both external cooling, and internal cooling via IV infusion of cooled saline. Benzodiazepines are used initially to control convulsions, with stronger anticonvulsants such as phenytoin or thiopental used if convulsions continue. Blood pressure can be lowered either with a combination of alpha blockers and beta blockers (or a mixed alpha/beta blocker), or with other drugs such as nifedipine or nitroprusside. Serotonin antagonists and dantrolene may be used as required. Despite the seriousness of the condition, the majority of patients survive if treatment is given in time, however, patients with a core body temperature over 40 °C at presentation tend to have a poor prognosis.

Pharmacology

PMA acts as a selective serotonin releasing agent (SSRA) with weak effects on dopamine and norepinephrine transporters. However, relative to MDMA, it is considerably less effective as a releaser of serotonin with properties more akin to a reuptake inhibitor in comparison. It evokes robust hyperthermia in rodents while producing only modest hyperactivity and serotonergic neurotoxicity, substantially lower than that caused by MDMA, and only at very high doses. Accordingly, it is not self-administered by rodents unlike amphetamine and MDMA, and anecdotal reports by humans suggest it is not particularly euphoric at all, perhaps even dysphoric in contrast. PMA has also been shown to act as a potent, reversible inhibitor of the enzyme MAO-A with no significant effects on MAO-B, and the combination of this property and serotonin release is likely responsible for its high lethality potential. The IC₅₀Tooltip half-maximal inhibitory concentration of PMA for MAO-A inhibition has been reported to be 300 to 600 nM.

It appears that PMA elevates body temperatures dramatically; the cause of this property is suspected to be related to its ability to inhibit MAO-A and at the same time releasing large amounts of serotonin, effectively causing serotonin syndrome. Amphetamines, especially serotonergic analogues such as MDMA, are strongly contraindicated to take with MAOIs. Many amphetamines and adrenergic compounds raise body temperatures, whereas some tend to produce more euphoric activity or peripheral vasoconstriction, and may tend to favor one effect over another. It appears that PMA activates the hypothalamus much more strongly than MDMA and other drugs like ephedrine, thereby causing rapid increases in body temperature (which is the major cause of death in PMA mortalities). Many people taking PMA try to get rid of the heat by taking off their clothes, taking cold showers or wrapping themselves in wet towels, and even sometimes by shaving off their hair.

History

PMA first came into circulation in the early 1970s, where it was used intentionally as a substitute for the hallucinogenic properties of LSD. It went by the street names of "Chicken Powder" and "Chicken Yellow" and was found to be the cause of a number of drug overdose deaths (the dosages taken being in the range of hundreds of milligrams) in the United States and Canada from that time. Between 1974 and the mid-1990s, there appear to have been no known fatalities from PMA.

Several deaths reported as MDMA-induced in Australia in the mid-1990s are now considered to have been caused by PMA, the users unaware that they were ingesting PMA and not MDMA as they had intended. There have been a number of PMA-induced deaths around the world since then.

In July 2013, seven deaths in Scotland were linked to tablets containing PMA that had been mis-sold as ecstasy and which had the Rolex crown logo on them. Several deaths in Northern Ireland, Particularly East Belfast were also linked to "Green Rolex" pills during that month.

In 2014, 2015 and early 2016, PMA sold as ecstasy was the cause of more deaths in the United States, United Kingdom, Netherlands, and Argentina. The pills containing the drug were reported to be red triangular tablets with a "Superman" logo.

The Red Ferarri pills are a new press of the Superman logo tablets that were reported to be found in Germany and Norway from 2016 to 2017.

Society and culture

Legal status

International

PMA is a Schedule I drug under the Convention on Psychotropic Substances.

Australia

PMA is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015). A Schedule 9 substance is a substance 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.

Finland

Substance is scheduled in decree of the government on amending the government decree on substances, preparations and plants considered to be narcotic drugs.

Germany

PMA is part of the Appendix 1 of the Betäubungsmittelgesetz. Therefore, owning and distribution of PMA is illegal.

Netherlands

On 13 June 2012 Edith Schippers, Dutch Minister of Health, Welfare and Sport, revoked the legality of PMA in the Netherlands after five deaths were reported in that year.

United Kingdom

PMA is a Class A drug in the UK.

United States

PMA is classified as a Schedule I hallucinogen under the Controlled Substances Act in the United States.

Economics

Distribution

Because PMA is given out through the same venues and distribution channels that MDMA tablets are, the risk of being severely injured, hospitalized or even dying from use of ecstasy increases significantly when a batch of ecstasy pills containing PMA starts to be sold in a particular area. PMA pills could be a variety of colours or imprints, and there is no way of knowing just from the appearance of a pill what drug(s) it might contain. Notable batches of pills containing PMA have included Louis Vuitton, Mitsubishi Turbo, Blue Transformers, Red/Blue Mitsubishi and Yellow Euro pills. Also PMA has been found in powder form.

Analogues

Four analogues of PMA have been reported to be sold on the black market, including PMMA, PMEA, 4-ETA and 4-MTA. These are the N-methyl, N-ethyl, 4-ethoxy and 4-methylthio analogues of PMA, respectively. PMMA and PMEA are anecdotally weaker, more "ecstasy-like" and somewhat less dangerous than PMA itself, but can still produce nausea and hyperthermia similar to that produced by PMA, albeit at slightly higher doses. 4-EtOA was briefly sold in Canada in the 1970s, but little is known about it. 4-MTA, however, is even more dangerous than PMA and produces strong serotonergic effects and intense hyperthermia, but with little to no euphoria, and was implicated in several deaths in the late 1990s.

See also

• 1-Aminomethyl-5-methoxyindane (AMMI)
• 2-Methoxyamphetamine (OMA)
• 3-Methoxyamphetamine (MMA)
• 4-Methylamphetamine (4-MA)
• 4-Ethoxyamphetamine (4-ETA)
• 4-Methylthioamphetamine (4-MTA)
• 4-Methoxy-N-ethylamphetamine (PMEA)
• 4-Methoxy-N-methylamphetamine (PMMA)
• 4-Hydroxy-N-methylamphetamine (pholedrine)
• Anisomycin

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. Drug Enforcement Administration October 2000. The Hallucinogen PMA: Dancing With Death Archived 2007-12-04 at the Wayback Machine
3. ^ Shulgin AT, Shulgin A (1991). "#97 4-MA". Pihkal: A Chemical Love Story. Transform Press. ISBN 978-0-9630096-0-9. Archived from the original on 2007-04-08. Retrieved 2005-12-11.
4. Karlis S (7 April 2008). "Warning of possible shift to killer drug". Sydney Morning Herald. Fairfax. Archived from the original on 2008-07-02. Retrieved 2008-06-29.
5. ^ Corrigall WA, Robertson JM, Coen KM, Lodge BA (January 1992). "The reinforcing and discriminative stimulus properties of para-ethoxy- and para-methoxyamphetamine". Pharmacology, Biochemistry, and Behavior. 41 (1): 165–169. CiteSeerX 10.1.1.670.6929. doi:10.1016/0091-3057(92)90077-S. PMID 1539067. S2CID 30080516.
6. Preve M, Suardi NE, Godio M, Traber R, Colombo RA (April 2017). "Paramethoxymethamphetamine (Mitsubishi turbo) abuse: Case report and literature review". European Psychiatry. 41 (S1): s875. doi:10.1016/j.eurpsy.2017.01.1762. S2CID 148876431.
7. Hegadoren KM, Martin-Iverson MT, Baker GB (April 1995). "Comparative behavioural and neurochemical studies with a psychomotor stimulant, an hallucinogen and 3,4-methylenedioxy analogues of amphetamine". Psychopharmacology. 118 (3): 295–304. doi:10.1007/BF02245958. PMID 7617822. S2CID 30756295.
8. Winter JC (February 1984). "The stimulus properties of para-methoxyamphetamine: a nonessential serotonergic component". Pharmacology, Biochemistry, and Behavior. 20 (2): 201–203. doi:10.1016/0091-3057(84)90242-9. PMID 6546992. S2CID 9673028.
9. "EcstasyData.org: Results : Lab Test Results for Recreational Drugs". www.ecstasydata.org. Archived from the original on 2015-02-15. Retrieved 2015-02-15.
10. ^ Davies C (10 July 2013). "Warning over fake ecstasy tablets after seven people die in Scotland". The Guardian. Archived from the original on 2 February 2020. Retrieved 10 July 2013.
11. ^ Barrell R (2 January 2015). "Four Dead Amid Fears Of Dodgy Batch Of 'Superman' Ecstasy Hitting The UK". HuffPost UK. Archived from the original on 21 April 2022. Retrieved 12 June 2022.
12. ^ Byard RW, Gilbert J, James R, Lokan RJ (September 1998). "Amphetamine derivative fatalities in South Australia--is "Ecstasy" the culprit?". The American Journal of Forensic Medicine and Pathology. 19 (3): 261–265. doi:10.1097/00000433-199809000-00013. PMID 9760094.
13. Waumans D, Bruneel N, Tytgat J (April 2003). "Anise oil as para-methoxyamphetamine (PMA) precursor". Forensic Science International. 133 (1–2): 159–170. doi:10.1016/S0379-0738(03)00063-X. PMID 12742705.
14. Martin TL (October 2001). "Three cases of fatal paramethoxyamphetamine overdose". Journal of Analytical Toxicology. 25 (7): 649–651. doi:10.1093/jat/25.7.649. PMID 11599618.
15. Becker J, Neis P, Röhrich J, Zörntlein S (March 2003). "A fatal paramethoxymethamphetamine intoxication". Legal Medicine. 5 (Suppl 1): S138–S141. doi:10.1016/s1344-6223(02)00096-2. PMID 12935573.
16. Smets G, Bronselaer K, De Munnynck K, De Feyter K, Van de Voorde W, Sabbe M (August 2005). "Amphetamine toxicity in the emergency department". European Journal of Emergency Medicine. 12 (4): 193–197. doi:10.1097/00063110-200508000-00010. PMID 16034267. S2CID 40206693.
17. Lora-Tamayo C, Tena T, Rodríguez A, Moreno D, Sancho JR, Enseñat P, Muela F (March 2004). "The designer drug situation in Ibiza". Forensic Science International. 140 (2–3): 195–206. doi:10.1016/j.forsciint.2003.11.021. PMID 15036441.
18. Dams R, De Letter EA, Mortier KA, Cordonnier JA, Lambert WE, Piette MH, et al. (1 July 2003). "Fatality due to combined use of the designer drugs MDMA and PMA: a distribution study". Journal of Analytical Toxicology. 27 (5): 318–322. doi:10.1093/jat/27.5.318. PMID 12908947.
19. Caldicott DG, Edwards NA, Kruys A, Kirkbride KP, Sims DN, Byard RW, et al. (2003). "Dancing with "death": p-methoxyamphetamine overdose and its acute management". Journal of Toxicology. Clinical Toxicology. 41 (2): 143–154. doi:10.1081/CLT-120019130. PMID 12733852. S2CID 39578828.
20. Menon MK, Tseng LF, Loh HH (May 1976). "Pharmacological evidence for the central serotonergic effects of monomethoxyamphetamines". The Journal of Pharmacology and Experimental Therapeutics. 197 (2): 272–279. PMID 946817.
21. ^ Hitzemann RJ, Loh HH, Domino EF (October 1971). "Effect of para-methoxyamphetamine on catecholamine metabolism in the mouse brain". Life Sciences. 10 (19 Pt. 1): 1087–1095. doi:10.1016/0024-3205(71)90227-x. PMID 5132700.
22. ^ Tseng LF, Menon MK, Loh HH (May 1976). "Comparative actions of monomethoxyamphetamines on the release and uptake of biogenic amines in brain tissue". The Journal of Pharmacology and Experimental Therapeutics. 197 (2): 263–271. PMID 1271280.
23. ^ Daws LC, Irvine RJ, Callaghan PD, Toop NP, White JM, Bochner F (August 2000). "Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 24 (6): 955–977. doi:10.1016/S0278-5846(00)00113-5. PMID 11041537. S2CID 24347904.
24. Green AL, El Hait MA (April 1980). "p-Methoxyamphetamine, a potent reversible inhibitor of type-A monoamine oxidase in vitro and in vivo". The Journal of Pharmacy and Pharmacology. 32 (4): 262–266. doi:10.1111/j.2042-7158.1980.tb12909.x. PMID 6103055. S2CID 42213032.
25. ^ Ask AL, Fagervall I, Ross SB (September 1983). "Selective inhibition of monoamine oxidase in monoaminergic neurons in the rat brain". Naunyn-Schmiedeberg's Archives of Pharmacology. 324 (2): 79–87. doi:10.1007/BF00497011. PMID 6646243. S2CID 403633.
26. Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK (2019). "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Front Pharmacol. 10: 1590. doi:10.3389/fphar.2019.01590. PMC 6989591. PMID 32038257.
27. Jaehne EJ, Salem A, Irvine RJ (July 2005). "Effects of 3,4-methylenedioxymethamphetamine and related amphetamines on autonomic and behavioral thermoregulation". Pharmacology, Biochemistry, and Behavior. 81 (3): 485–496. doi:10.1016/j.pbb.2005.04.005. PMID 15904952. S2CID 9680452.
28. Callaghan PD, Irvine RJ, Daws LC (October 2005). "Differences in the in vivo dynamics of neurotransmitter release and serotonin uptake after acute para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine revealed by chronoamperometry". Neurochemistry International. 47 (5): 350–361. doi:10.1016/j.neuint.2005.04.026. PMID 15979209. S2CID 23372945.
29. Jaehne EJ, Salem A, Irvine RJ (September 2007). "Pharmacological and behavioral determinants of cocaine, methamphetamine, 3,4-methylenedioxymethamphetamine, and para-methoxyamphetamine-induced hyperthermia". Psychopharmacology. 194 (1): 41–52. doi:10.1007/s00213-007-0825-9. PMID 17530474. S2CID 25420902.
30. Refstad S (November 2003). "Paramethoxyamphetamine (PMA) poisoning; a 'party drug' with lethal effects". Acta Anaesthesiologica Scandinavica. 47 (10): 1298–1299. doi:10.1046/j.1399-6576.2003.00245.x. PMID 14616331. S2CID 28006785.
31. DEA. "The Hallucinogen PMA: Dancing With Death" (PDF). Archived (PDF) from the original on 2008-06-23. Retrieved 2008-06-29.
32. Felgate HE, Felgate PD, James RA, Sims DN, Vozzo DC (1 March 1998). "Recent paramethoxyamphetamine deaths". Journal of Analytical Toxicology. 22 (2): 169–172. doi:10.1093/jat/22.2.169. PMID 9547415.
33. Galloway JH, Forrest AR (September 2002). "Caveat Emptor: Death involving the use of 4-methoxyamphetamine". Journal of Clinical Forensic Medicine. 9 (3): 160. doi:10.1016/S1353-1131(02)00043-3. PMID 15274949.
34. Lamberth PG, Ding GK, Nurmi LA (April 2008). "Fatal paramethoxy-amphetamine (PMA) poisoning in the Australian Capital Territory". The Medical Journal of Australia. 188 (7): 426. doi:10.5694/j.1326-5377.2008.tb01695.x. PMID 18393753. S2CID 11987961.
35. "Renewed warning over 'Rolex' pills". BBC News. 24 July 2013. Archived from the original on 11 September 2018. Retrieved 10 September 2018.
36. "WATCH OUT FOR DANGEROUS SUPERMAN PILL - News - Deep House Amsterdam". deephouseamsterdam.com. 30 January 2014. Archived from the original on 2 January 2015. Retrieved 2 January 2015.
37. "¿Qué es Superman, la droga que ya ha cobrado varias vidas en el mundo?" [What is Superman, the drug that has already claimed several lives in the world?]. ElPais [The Country] (in Spanish). 18 April 2016. Archived from the original on 19 April 2016. Retrieved 19 April 2016.
38. "Las claves para entender qué pasó". La Nación. 2016-04-17. Archived from the original on 2016-04-18. Retrieved 2016-04-19.
39. "Drug Warning – Reagent Tests UK". www.reagent-tests.uk. Archived from the original on 2018-09-11. Retrieved 2017-07-05.
40. "Annual Estimates Of Requirements Of Narcotic Drugs, Manufacture Of Synthetic Drugs, Opium Production And Cultivation Of The…" (PDF). Archived from the original (PDF) on 2012-08-31. Retrieved 2008-06-15.
41. ^ Poisons Standard October 2015 https://www.comlaw.gov.au/Details/F2015L01534 Archived 2016-01-19 at the Wayback Machine
42. "Valtioneuvoston asetus huumausaineina pidettävistä aineista, valmisteista ja kasveista annetun valtioneuvoston asetuksen muuttamisesta" [Decree of the Government on amending the government decree on substances, preparations and plants considered to be narcotic drugs]. Finlex (in Finnish). Helsinki: Finland's Ministry of Justice. 25 October 2018. Archived from the original on 26 March 2023. Retrieved 8 April 2023.
43. "Valtioneuvoston asetus huumausaineina pidettävistä aineista, valmisteista ja kasveista annetun valtioneuvoston asetuksen muuttamisesta" [Decree of the Government on amending the government decree on substances, preparations and plants considered to be narcotic drugs]. Finlex (in Finnish). Helsinki: Finland's Ministry of Justice. 13 January 2022. Archived from the original on 24 March 2023. Retrieved 8 April 2023.
44. "Doden na gebruik speed met 4-MA" [Deaths after using speed 4-MA] (in Dutch). 13 June 2012. Archived from the original on 16 June 2012. Retrieved 13 June 2012.
45. "List of Controlled Drugs". Release (agency). 2013-08-13. Archived from the original on 2024-04-29. Retrieved 2024-04-29.
46. 21 CFR 1308.11 Archived 2009-08-27 at the Wayback Machine
47. Galloway JH, Forrest AR (September 2002). "Caveat Emptor: Death involving the use of 4-methoxyamphetamine". Journal of Clinical Forensic Medicine. 9 (3): 160. doi:10.1016/s1353-1131(02)00043-3. PMID 15274949.
48. "Drug Info". Archived from the original on 2008-05-29. Retrieved 2008-06-15.
49. "Warning: pills sold as ecstasy found to contain PMA". Archived from the original on 2008-06-22. Retrieved 2008-06-15.
50. Chamberlin T, Murray D. NET Syndicated QLD News 'Louis Vuitton' designer death drug hits the streets Archived 2012-09-28 at the Wayback Machine
51. Kraner JC, McCoy DJ, Evans MA, Evans LE, Sweeney BJ (October 2001). "Fatalities caused by the MDMA-related drug paramethoxyamphetamine (PMA)". Journal of Analytical Toxicology. 25 (7): 645–648. doi:10.1093/jat/25.7.645. PMID 11599617.
52. Casale JF, Hays PA, Spratley TK, Smith PR (2006). "The Characterization of 4-Methoxy-N-ethylamphetamine Hydrochloride". Microgram Journal. 4 (1–4): 42–46.

External links

• Erowid.org - PMA
• PiHKAL PMA entry
• PMA entry in PiHKAL • info
• Death drug may become health crisis, news.ninemsn.com.au article, Issued 22 February 2007.

• Drugs not assigned an ATC code
• Substituted amphetamines
• Monoamine oxidase inhibitors
• Designer drugs
• Serotonin releasing agents
• Serotonin receptor agonists
• 4-Methoxyphenyl compounds