MiPLA
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| Other names | MiPLA; MIPLA; Lysergic acid methylisopropylamide; N-Methyl-N-isopropyllysergamide |
| Routes of administration | Oral[1][2] |
| Drug class | Serotonin receptor modulator; 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen |
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| Formula | C20H25N3O |
| Molar mass | 323.440 g·mol−1 |
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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).[4][1] It is taken orally.[1][2] 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.[4][1][5] It is only somewhat less potent than LSD.[1][2]
Use and effects
[edit]MiPLA has about one-third to one-half of the potency of LSD in producing psychedelic effects in humans.[1][2] 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.[1][2]
MiPLA and its homologue EiPLA are the only known simple N,N-dialkyllysergamides that approach the potency of LSD itself.[4] All other N,N-dialkyl analogues tested, including the dimethyl, dipropyl, methylethyl, and so on, are only around one-tenth as potent as LSD.[6] However, some N-monoalkyllysergamides, such as the sec-butyl and tert-butyl derivatives, were also found to show activity and potency comparable to LSD.[7] In addition, iPLA, the N-monoisopropyl derivative, is only slightly weaker than MiPLA.[8][9]
Interactions
[edit]Pharmacology
[edit]Pharmacodynamics
[edit]MiPLA has been found to interact with serotonin receptors, including acting as an agonist of the serotonin 5-HT2A receptor.[10][9][1] It fully substitutes for LSD in rodent drug discrimination tests with only slightly lower potency than LSD.[9][1] In addition, MiPLA produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, with about one-third the potency of LSD.[1] The drug showed roughly the same potency in producing the head-twitch response as EcPLA.[1]
Chemistry
[edit]MiPLA is a structural isomer of LSD, with the alkyl groups on the amide nitrogen having been subjected to a methylene shuffle.[5]
Synthesis
[edit]The chemical synthesis of MiPLA has been described.[11]
Analogues
[edit]Analogues of MiPLA include iPLA, EiPLA, EPLA, EcPLA, DiPLA, LSB, and LSP, among others.[10] The ester derivatives 1P-MiPLA and 1cP-MiPLA are thought to be prodrugs of MiPLA.[5][12][13]
History
[edit]MiPLA was originally discovered and described by Albert Hofmann at Sandoz during the original structure–activity research into LSD.[7] It has subsequently been investigated in more detail by the team led by David E. Nichols at Purdue University.[1][4] 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.[8] MiPLA was first encountered as a novel designer drug by 2018.[1]
Society and culture
[edit]Legal status
[edit]Austria
[edit]MiPLA is technically not illegal in Austria but it may fall in the NPSG (Neue-Psychoaktive-Substanzen-Gesetz Österreich) as an analogue of LSD.[citation needed]
France
[edit]MiPLA is illegal in France.[3]
Germany
[edit]MiPLA is controlled in Germany under the NpSG (New Psychoactive Substances Act)[14] as of July 18, 2019.[15] 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.[16]
Switzerland
[edit]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.[17]
United Kingdom
[edit]MiPLA is a controlled substance in the United Kingdom via the Psychoactive Substances Act 2016.[citation needed]
United States
[edit]MiPLA is not scheduled in the United States 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.[citation needed] However, it may be a Schedule I controlled substance in the United States due to being a skeletal isomer[5] of LSD.[citation needed]
See also
[edit]References
[edit]- ^ a b c d e f g h i j k l m Halberstadt AL, Klein LM, Chatha M, Valenzuela LB, Stratford A, Wallach J, Nichols DE, Brandt SD (February 2019). "Pharmacological characterization of the LSD analog N-ethyl-N-cyclopropyl lysergamide (ECPLA)". Psychopharmacology (Berl). 236 (2): 799–808. doi:10.1007/s00213-018-5055-9. PMC 6848745. PMID 30298278.
- ^ a b c d e 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]
- ^ a b "Arrêté du 20 mai 2021 modifiant l'arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants". www.legifrance.gouv.fr (in French). 20 May 2021.
- ^ a b c d Huang X, Marona-Lewicka D, Pfaff RC, Nichols DE (March 1994). "Drug discrimination and receptor binding studies of N-isopropyl lysergamide derivatives". Pharmacology Biochemistry and Behavior. 47 (3): 667–673. doi:10.1016/0091-3057(94)90172-4. PMID 8208787. S2CID 16490010.
- ^ a b c d Wachełko O, Nowak K, Tusiewicz K, Zawadzki M, Szpot P (January 2025). "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. doi:10.1039/d4an01361a. PMID 39636448.
- ^ Hofmann A (June 1959). "Psychotomimetic drugs; chemical and pharmacological aspects" (PDF). Acta Physiologica et Pharmacologica Neerlandica. 8: 240–258. PMID 13852489.
- ^ a b US patent 2997470, Pioch RP, "Lysergic Acid Amides", published 1956-03-05, issued 1961-08-22
- ^ a b Nichols DE (2001). "LSD and its lysergamide cousins" (PDF). The Heffter Review of Psychedelic Research. 2. Santa Fe, New Mexico: Heffter Research Institute: 80–87.
- ^ a b c Pfaff RC, Huang X, Marona-Lewicka D, Oberlender R, Nichols DE (1994). "Lysergamides revisited" (PDF). NIDA Research Monograph. 146: 52–73. PMID 8742794.
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) [...]
- ^ a b Nichols DE (2018). Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524.
- ^ Shoda T, Tsuji G, Kawamura M, Kurohara T, Misawa T, Kikura-Hanajiri R, Demizu Y (June 2024). "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. doi:10.1002/dta.3586. PMID 37830386.
- ^ Tusiewicz K, Wachełko O, Zawadzki M, Szpot P (December 2024). "Forensic Aspects of Designer LSD Analogs Identification by GC-MS (EI) and UV Spectroscopy". Molecules. 29 (23): 5717. doi:10.3390/molecules29235717. PMC 11643092. PMID 39683876.
- ^ Tanaka R, Kawamura M, Mizutani S, Kikura-Hanajiri R (July 2023). "Identification of LSD analogs, 1cP-AL-LAD, 1cP-MIPLA, 1V-LSD and LSZ in sheet products". Forensic Toxicol. 41 (2): 294–303. doi:10.1007/s11419-023-00661-1. PMC 10310582. PMID 36809464.
- ^ "Anlage NpSG" (in German). Bundesministerium der Justiz und für Verbraucherschutz [Federal Ministry of Justice and Consumer Protection]. Retrieved December 10, 2019.
- ^ "Verordnung zur Änderung der Anlage des Neue-psychoaktive-Stoffe-Gesetzes und von Anlagen des Betäubungsmittelgesetzes" (PDF). Bundesgesetzblatt Jahrgang 2019 Teil I Nr. 27 (in German). Bundesanzeiger Verlag. July 17, 2019. pp. 1083–1094. Retrieved January 1, 2020.
- ^ "§ 4 NpSG" (in German). Bundesministerium der Justiz und für Verbraucherschutz [Federal Ministry of Justice and Consumer Protection]. Retrieved December 10, 2019.
- ^ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020.