Chemistry:MiPLA

From HandWiki

MiPLA, also known as N-methyl-N-isopropyllysergamide or as lysergic acid methylisopropylamide, is a psychedelic drug of the lysergamide family related to lysergic acid diethylamide (LSD).[1][2] It is taken orally.[2][3] The drug is a structural isomer of LSD in which the N,N-diethyl groups have been replaced with N-methyl and N-isopropyl groups.[1][2][4] It is only somewhat less potent than LSD as a psychedelic.[2][3] MiPLA has been encountered as a novel designer drug.[2][5][6][7]

Use and effects

MiPLA has about 33% to 50% of the potency of LSD in producing psychedelic effects in humans.[2][3] According to Alexander Shulgin, it produced LSD-like effects at a dose of 180 to 300 μg orally, compared to a dose range of 60 to 200 μg in the case of LSD.[2][3] Elsewhere, the following has been described about the properties and effects of MiPLA:[8]

"The primary route of administration for MiPLA is orally. Users report that, despite its lower potency, the hallucinogenic effects of MiPLA are very similar to those of LSD. Users typically describe it as "...soft LSD..." However, some reports indicate that the after-effects are harsh and negative. Active doses range from 50 to 300 mcg, depending on the desired effects. Effects occur within 20 to 40 minutes and last for 4 to 6 hours. It is sold recreationally as blotters or powder."[8]

MiPLA and its homologue EiPLA are the only known simple N,N-dialkyllysergamides that approach the potency of LSD itself.[1] All other N,N-dialkyl analogues tested, including the dimethyl, dipropyl, methylethyl, and so on, are only around one-tenth as potent as LSD.[9] However, some N-monoalkyllysergamides, such as the sec-butyl and tert-butyl derivatives, were also found to show activity and potency comparable to LSD.[10] In addition, iPLA, the N-monoisopropyl derivative, is only slightly weaker than MiPLA.[11][12]

Interactions

Pharmacology

Pharmacodynamics

MiPLA has been found to interact with serotonin receptors, including acting as an agonist of the serotonin 5-HT2A receptor.[13][14][1][12][2][15][16][17][18] It also interacts with the dopamine D1 and D2 receptors.[16][15] The drug fully substitutes for LSD in rodent drug discrimination tests with only slightly lower potency than LSD.[12][1][2][19] In addition, MiPLA produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, with about one-third the potency of LSD.[2][19] The drug showed roughly the same potency in producing the head-twitch response as EcPLA.[2]

Chemistry

MiPLA, also known as N-methyl-N-isopropyllysergamide or as lysergic acid methylisopropylamide, is a substituted lysergamide and a structural isomer of lysergic acid diethylamide (LSD; N,N-diethyllysergamide), with the alkyl groups on the amide nitrogen having been subjected to a methylene shuffle.[4]

Synthesis

The chemical synthesis of MiPLA has been described.[10][7]

Analogues

Analogues of MiPLA include iPLA, EiPLA, EPLA, EcPLA, DiPLA, LSB, and LSP, among others.[13] The ester derivatives 1P-MiPLA and 1cP-MiPLA are thought to be prodrugs of MiPLA.[4][20][21]

History

MiPLA was originally discovered and described by Albert Hofmann at Sandoz during the original structure–activity research into LSD, with Eli Lilly and Company filing a patent in 1956 and it being published in 1961.[10] It was subsequently investigated in more detail by the team led by David E. Nichols at Purdue University in the 1990s.[2][12][1] The main use for this drug has been in studies of the binding site at the serotonin 5-HT2A receptor through which LSD produces its hallucinogenic effects.[11] MiPLA was first encountered as a novel designer drug by 2018.[2][5][6][7]

Society and culture

Austria

Canada

MiPLA is not a controlled substance in Canada as of 2025.[22]

France

MiPLA is illegal in France.[23]

Germany

MiPLA is controlled in Germany under the NpSG (New Psychoactive Substances Act)[24] as of July 18, 2019.[25] Production and import with the aim to place it on the market, administration to another person and trading is punishable. Possession is illegal but not penalized.[26]

Switzerland

MiPLA can be considered a controlled substance in Switzerland as a defined derivative of Lysergic Acid under Verzeichnis E point 263. It is legal when used for scientific or industrial use.[27]

United Kingdom

United States

MiPLA is not scheduled in the United States,[28] but may be considered to be an analogue of LSD, which would make it illegal to possess for human consumption under the Federal Analogue Act. However, it may be a Schedule I controlled substance in the United States due to being an isomer of LSD.[4][29]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "Drug discrimination and receptor binding studies of N-isopropyl lysergamide derivatives". Pharmacology Biochemistry and Behavior 47 (3): 667–673. March 1994. doi:10.1016/0091-3057(94)90172-4. PMID 8208787. 
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 "Pharmacological characterization of the LSD analog N-ethyl-N-cyclopropyl lysergamide (ECPLA)". Psychopharmacology (Berl) 236 (2): 799–808. February 2019. doi:10.1007/s00213-018-5055-9. PMID 30298278. 
  3. ↑ 3.0 3.1 3.2 3.3 Shulgin AT (2016) Pharmacology notebook 9. Available online: https://www.erowid.org/library/books_online/shulgin_labbooks/shulgin_pharmacology_notebook9_searchable.pdf [Accessed: January 20, 2018]
  4. ↑ 4.0 4.1 4.2 4.3 "A highly sensitive UHPLC-MS/MS method for determining 15 designer LSD analogs in biological samples with application to stability studies". Analyst 150 (2): 290–308. January 2025. doi:10.1039/d4an01361a. PMID 39636448. 
  5. ↑ 5.0 5.1 "シート状危険ドラッグ製品中のLSD誘導体1cP-LSD, MIPLA, 1B-LSDの同定" (in Japanese). Yakugaku Zasshi 140 (11): 1405–1413. 2020. doi:10.1248/yakushi.20-00124. PMID 33132277. 
  6. ↑ 6.0 6.1 "Separating the wheat from the chaff: Observations on the analysis of lysergamides LSD, MIPLA, and LAMPA". Drug Test Anal 14 (3): 545–556. March 2022. doi:10.1002/dta.3103. PMID 34022102. 
  7. ↑ 7.0 7.1 7.2 "Structural analysis of an lysergic acid diethylamide (LSD) analogue N-methyl-N-isopropyllysergamide (MiPLA): Insights from Rotamers in NMR spectra". Drug Test Anal 16 (6): 588–594. June 2024. doi:10.1002/dta.3586. PMID 37830386. 
  8. ↑ 8.0 8.1 "MIPLA (Метилизопропиллизергамид)" (in ru). https://aipsin.com/newsubstance/843/. 
  9. ↑ "Psychotomimetic drugs; chemical and pharmacological aspects". Acta Physiologica et Pharmacologica Neerlandica 8: 240–258. June 1959. PMID 13852489. https://www.samorini.it/doc1/alt_aut/ek/hofmann-psychotomimetic-drugs.pdf. 
  10. ↑ 10.0 10.1 10.2 Pioch RP, "Lysergic Acid Amides", US patent 2997470, published 1956-03-05, issued 1961-08-22
  11. ↑ 11.0 11.1 "LSD and its lysergamide cousins.". The Heffter Review of Psychedelic Research (Santa Fe, New Mexico: Heffter Research Institute) 2: 80–87. 2001. https://www.thevespiary.org/rhodium/Rhodium/Vespiary/talk/files/5022-chap6c758.pdf. 
  12. ↑ 12.0 12.1 12.2 12.3 "Lysergamides revisited". NIDA Research Monograph 146: 52–73. 1994. PMID 8742794. https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=57. Retrieved 2025-10-22. "The series of isopropyl amides has recently been completed with the synthesis of the N-isopropyl, in addition to the N-methyl-N-isopropyl, N-ethyl-N-isopropyl, and the N,N-diisopropyl, as shown in figure 12. With the exception of the N,N-diisopropylamide, all compounds completely substitute in the DD paradigm in rats trained to discriminate LSD from saline. In table 6, the receptor-binding data for displacement of [3H]-ketanserin from rat cortical homogenate are shown. [...] TABLE 6. Radioligand binding data for N-methyl-N-isopropyl lysergamides: [3H]-ketanserin displacement (unpublished results) [...]". 
  13. ↑ 13.0 13.1 Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences. 36. 2018. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. https://bitnest.netfirms.com/external/10.1007/7854_2017_475. 
  14. ↑ "Structure–activity relationships of serotonin 5-HT2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling 1 (5): 559–579. 2012. doi:10.1002/wmts.42. ISSN 2190-460X. 
  15. ↑ 15.0 15.1 "LSD and structural analogs: pharmacological evaluation at D1 dopamine receptors". Psychopharmacology (Berl) 118 (4): 401–409. April 1995. doi:10.1007/BF02245940. PMID 7568626. 
  16. ↑ 16.0 16.1 McCorvy JD (16 January 2013). Mapping the binding site of the 5-HT2A receptor using mutagenesis and ligand libraries: Insights into the molecular actions of psychedelics (Ph.D. thesis). Purdue University. Archived from the original on 15 May 2025. Retrieved 27 May 2025 – via Purdue e-Pubs.{{cite thesis}}: CS1 maint: bot: original URL status unknown (link)
  17. ↑ "Toward a molecular understanding of hallucinogen action". 30 October 2007. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=5ead04596d21b2918cbacd6d21744aab9f51684e. 
  18. ↑ Braden MR (2007). Towards a biophysical understanding of hallucinogen action (Ph.D. thesis). Purdue University. ProQuest 304838368.
  19. ↑ 19.0 19.1 "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species". Neuropharmacology 167. May 2020. doi:10.1016/j.neuropharm.2019.107933. PMID 31917152. 
  20. ↑ "Forensic Aspects of Designer LSD Analogs Identification by GC-MS (EI) and UV Spectroscopy". Molecules 29 (23): 5717. December 2024. doi:10.3390/molecules29235717. PMID 39683876. 
  21. ↑ "Identification of LSD analogs, 1cP-AL-LAD, 1cP-MIPLA, 1V-LSD and LSZ in sheet products". Forensic Toxicol 41 (2): 294–303. July 2023. doi:10.1007/s11419-023-00661-1. PMID 36809464. 
  22. ↑ "Controlled Drugs and Substances Act". https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html. 
  23. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named LegiFrance
  24. ↑ "Anlage NpSG" (in de). Bundesministerium der Justiz und für Verbraucherschutz [Federal Ministry of Justice and Consumer Protection]. https://www.gesetze-im-internet.de/npsg/anlage.html. 
  25. ↑ "Verordnung zur Änderung der Anlage des Neue-psychoaktive-Stoffe-Gesetzes und von Anlagen des Betäubungsmittelgesetzes" (in de). Bundesgesetzblatt Jahrgang 2019 Teil I Nr. 27. Bundesanzeiger Verlag. July 17, 2019. pp. 1083–1094. http://www.bgbl.de/xaver/bgbl/start.xav?startbk=Bundesanzeiger_BGBl&jumpTo=bgbl119s1083.pdf. 
  26. ↑ "§ 4 NpSG" (in de). Bundesministerium der Justiz und für Verbraucherschutz [Federal Ministry of Justice and Consumer Protection]. https://www.gesetze-im-internet.de/npsg/__4.html. 
  27. ↑ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in de). Bundeskanzlei [Federal Chancellery of Switzerland]. https://www.admin.ch/opc/de/classified-compilation/20101220/index.html. 
  28. ↑ Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026, https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf 
  29. ↑ Drug Enforcement Administration (3 December 2007). "Definition of “Positional Isomer” as It Pertains to the Control of Schedule I Controlled Substances". https://www.federalregister.gov/documents/2007/12/03/E7-23413/definition-of-positional-isomer-as-it-pertains-to-the-control-of-schedule-i-controlled-substances. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:MiPLA&oldid=4246988"