Lysergic acid 2,4-dimethylazetidide

Last updated
Lysergic acid 2,4-dimethylazetidide
LSD-azetidine.svg
Clinical data
Other namesLysergic acid 2,4-dimethylazetidine, Diazedine, Lambda, LSZ
Routes of
administration 		Oral
Legal status
Legal status
  • DE: NpSG (Industrial and scientific use only)
  • UK: Class A
  • Illegal in Denmark, France, [1] Sweden and Switzerland
Identifiers
  • [(6aR,9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-yl]-[(2S,4S)-2,4-dimethylazetidin-1-yl]methanone
​
  • freebase:(S,S)-isomer, freebase
  • tartrate salt:(S,S)-isomer, tartrate salt
CAS Number
  • freebase: 470666-31-0 Yes check.svgY
  • tartrate salt: 470666-32-1 X mark.svgN
PubChem CID
ChemSpider
UNII
Chemical and physical data
Formula C21H25N3O
Molar mass 335.451 g·mol−1
3D model (JSmol)
  • freebase: C[C@H]1C[C@@H](N1C(=O)[C@H]2CN([C@@H]3CC4=CNC5=CC=CC(=C45)C3=C2)C)C
  • freebase: InChI=1S/C21H25N3O/c1-12-7-13(2)24(12)21(25)15-8-17-16-5-4-6-18-20(16)14(10-22-18)9-19(17)23(3)11-15/h4-6,8,10,12-13,15,19,22H,7,9,11H2,1-3H3/t12-,13-,15+,19+/m0/s1 X mark.svgN
  • Key:DUKNIHFTDAXJON-CTQRGLTFSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Lysergic acid 2,4-dimethylazetidide (LA-SS-Az, LSZ) is an analog of LSD developed by the team led by David E. Nichols at Purdue University. [2] [3] It was developed as a rigid analog of LSD with the diethylamide group constrained into an azetidine ring in order to map the binding site at the 5-HT2A receptor. There are three possible stereoisomers around the azetidine ring, with the (S,S)-(+) isomer being the most active, slightly more potent than LSD itself in drug discrimination tests using trained rats. [4]

Contents

There have been several unconfirmed reports of lysergic acid 2,4-dimethylazetidide being synthesized in illicit laboratories and distributed on blotter paper or in liquid solution under names such as "diazedine" and "λ". [5] [6]

In 2013 LSZ also appeared on some designer drug and research chemical markets in the UK. [7] [ unreliable source? ][ unreliable source? ] [8] LSZ later gained international popularity through a small cluster of mail-order novel psychedelic shops that appeared in 2012. [9]

On June 10, 2014 the UK Advisory Council on the Misuse of Drugs (ACMD) recommended that LSZ be specifically named in the UK Misuse of Drugs Act as a class A drug despite not identifying any harm associated with its use. [8] The UK Home office accepted this advice and announced a ban of the substance to be enacted on 6 January 2015 as part of The Misuse of Drugs Act 1971 (Amendment) (No. 2) Order 2014.

LSZ is illegal in Switzerland as of December 2015, [10] in Denmark as of May 2015, [11] and in Sweden as of January 26, 2016. [12]

See also

Related Research Articles

Lysergic acid diethylamide Hallucinogenic drug

Lysergic acid diethylamide (LSD), also known colloquially as acid, is a psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily visual, as well as auditory, hallucinations. Dilated pupils, increased blood pressure, and increased body temperature are typical. Since LSD binds to dopamine receptors in addition to serotonin receptors, its effects are also more energetic and fast-paced compared to psychedelics such as psilocybin, which is not a dopamine agonist. Effects typically begin within half an hour and can last for up to 20 hours. LSD is also capable of occasioning mystical experiences and ego dissolution, albeit less frequently than compounds such as psilocybin. It is used mainly as a recreational drug or for spiritual reasons. LSD is both the prototypical psychedelic and one of the 'classical' psychedelics, being the psychedelics with the greatest scientific and cultural significance.

Lysergamides

Amides of lysergic acid are collectively known as lysergamides, and include a number of compounds with potent agonist and/or antagonist activity at various serotonin and dopamine receptors.

ALD-52 Chemical compound

ALD-52, also known as 1-acetyl-LSD, is a chemical analogue of lysergic acid diethylamide (LSD). It was originally discovered by Albert Hofmann in 1957 but was not widely studied until the rise in popularity of psychedelics in the 1960s.

Lysergic acid hydroxyethylamide

D-Lysergic acid α-hydroxyethylamide, also known as D-lysergic acid methyl carbinolamide, is an alkaloid of the ergoline family, believed to be present in small amounts in various species in the Convolvulaceae, as well as some species of fungi.

AL-LAD

AL-LAD, also known as 6-allyl-6-nor-LSD, is a psychedelic drug and an analog of lysergic acid diethylamide (LSD). It is described by Alexander Shulgin in the book TiHKAL. It is synthesized starting from nor-LSD as a precursor, using allyl bromide as a reactant.

ETH-LAD Chemical compound

ETH-LAD, 6-ethyl-6-nor-lysergic acid diethylamide is an analogue of LSD. Its human psychopharmacology was first described by Alexander Shulgin in the book TiHKAL. ETH-LAD is a psychedelic drug similar to LSD, and is slightly more potent than LSD itself, with an active dose reported at between 20 and 150 micrograms. ETH-LAD has subtly different effects to LSD, described as less demanding.

PRO-LAD

PRO-LAD is an analogue of LSD. It is described by Alexander Shulgin in the book TiHKAL. PRO-LAD is a psychedelic drug similar to LSD, and is around as potent as LSD itself with an active dose reported at between 100 and 200 micrograms.

BU-LAD

BU-LAD, also known as 6-butyl-6-nor-lysergic acid diethylamide, is an analogue of LSD first made by Alexander Shulgin and reported in the book TiHKAL. BU-LAD is a psychedelic drug similar to LSD, but is significantly less potent than LSD, with a dose of 500 micrograms producing only mild effects.

LSM-775

N-Morpholinyllysergamide (LSM-775) is a derivative of ergine. It is less potent than LSD but is reported to have some LSD-like effects at doses ranging from 75 to 700 micrograms and a shorter duration. There are fewer signs of cardiovascular stimulation and peripheral toxicity with LSM-775 compared to LSD.

Methylisopropyllysergamide

Methylisopropyllysergamide is an analogue of LSD that was originally discovered by Albert Hofmann at Sandoz during the original structure-activity research into LSD. It has subsequently been investigated in more detail by the team led by David E. Nichols at Purdue University. Methylisopropyllysergamide is a structural isomer of LSD, with the alkyl groups on the amide nitrogen having been subjected to a methylene shuffle. MIPLA and its ethylisopropyl homologue are the only simple N,N-dialkyl lysergamides that approach the potency of LSD itself, being around 1/3-1/2 the potency of LSD, while all other dialkyl analogues tested are only around 1/10 as potent as LSD, although some N-monoalkyl lysergamides such as the sec-butyl and t-butyl derivatives were also found to show an activity profile and potency comparable to LSD, and the mono-isopropyl derivative is only slightly weaker than MIPLA. Apart from its lower potency, the hallucinogenic effects of methylisopropyllysergamide are similar to those of LSD itself, and the main use for this drug has been in studies of the binding site at the 5-HT2A receptor through which LSD exerts most of its pharmacological effects.

Lysergic acid 2-butyl amide

Lysergic acid 2-butyl amide (2-Butyllysergamide, LSB) is an analogue of LSD originally developed by Richard Pioch at Eli Lilly in the 1950s, but mostly publicised through research conducted by the team led by David E. Nichols at Purdue University. It is a structural isomer of LSD, with the two ethyl groups on the amide nitrogen having been replaced by a single sec-butyl group, joined at the 2-position. It is one of the few lysergamide derivatives to exceed the potency of LSD in animal drug discrimination assays, with the (R) isomer having an ED50 of 33nmol/kg for producing drug-appropriate responding, vs 48nmol/kg for LSD itself. The corresponding (R)-2-pentyl analogue has higher binding affinity for the 5-HT1A and 5-HT2A receptors, but is less potent in producing drug-appropriate responding, suggesting that the butyl compound has a higher efficacy at the receptor target. The drug discrimination assay for LSD in rats involves both 5-HT1A and 5-HT2A mediated components, and while lysergic acid 2-butyl amide is more potent than LSD as a 5-HT1A agonist, it is slightly less potent as a 5-HT2A agonist, and so would probably be slightly less potent than LSD as a hallucinogen in humans. The main use for this drug has been in studies of the binding site at the 5-HT2A receptor through which LSD exerts most of its pharmacological effects, with the stereoselective activity of these unsymmetric monoalkyl lysergamides foreshadowing the subsequent development of compounds such as lysergic acid 2,4-dimethylazetidide (LSZ).

LSD-Pip Compound related to LSD

LSD-Pip is a compound from the ergoline family, related to LSD but with the N,N-diethyl substitution replaced by a piperidine group. It is more potent than the corresponding pyrrolidine and morpholine analogues, but is still several times less potent than LSD as a 5-HT2A agonist. Early studies suggested this compound to be inactive as a psychedelic in humans, though this does not seem to have been confirmed by any more recent work.

6-Isopropyl-6-nor-lysergic acid diethylamide

6-Isopropyl-6-nor-lysergic acid diethylamide (IP-LAD) is an analog of lysergic acid diethylamide (LSD) developed by the team of David E. Nichols. In studies on mice, it was found to be approximately 40% the potency of LSD, compared to the 60% increase in potency seen with ETH-LAD and roughly equivalent potency in AL-LAD and PRO-LAD.

1P-LSD

1P-LSD or 1-propionyl-lysergic acid diethylamide is a psychedelic drug of the lysergamide class that is a derivative and functional analogue of LSD and a homologue of ALD-52. It has been sold online as a designer drug since 2015. It modifies the LSD molecule by adding a propionyl group to the nitrogen molecule of LSD's indole.

1P-ETH-LAD Chemical compound

1P-ETH-LAD is an analog of LSD. 1P-ETH-LAD is a psychedelic drug similar to LSD. Research has shown formation of ETH-LAD from 1P-ETH-LAD incubated in human serum, suggesting that it functions as a prodrug. It is part of the lysergamide chemical class. Like ETH-LAD, this drug has been reported to be significantly more potent than LSD itself, and is reported to largely mimic ETH-LAD's psychedelic effects.

ECPLA

ECPLA (N-ethyl-N-cyclopropyllysergamide) is an analog of lysergic acid diethylamide (LSD) developed by Synex Synthetics. In studies in mice, it was found to have approximately 40% the potency of LSD.

ETFELA

ETFELA is an analog of lysergic acid diethylamide (LSD) first synthesised by Jason C. Parrish as part of the research team led by David E. Nichols. In studies in vitro, it was found to be slightly more potent than LSD itself.

1cP-LSD

1cP-LSD is an acylated derivative of lysergic acid diethylamide (LSD), which has been sold as a designer drug. In tests on mice it was found to be an active psychedelic with similar potency to 1P-LSD.

1B-LSD

1B-LSD is an acylated derivative of lysergic acid diethylamide (LSD), which has been sold as a designer drug. In tests on mice it was found to be an active psychedelic, though with only around 1/7th the potency of LSD itself.

References

  1. ↑ "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.
  2. ↑ Brandt SD, Kavanagh PV, Westphal F, Elliott SP, Wallach J, Colestock T, et al. (January 2017). "6 -allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ)" (PDF). Drug Testing and Analysis. 9 (1): 38–50. doi:10.1002/dta.1985. PMC   5411264 . PMID   27265891.
  3. ↑ Schifano F, Orsolini L, Papanti D, Corkery J (June 2016). "NPS: Medical Consequences Associated with Their Intake". Neuropharmacology of New Psychoactive Substances (NPS). Current Topics in Behavioral Neurosciences. 32. Springer International Publishing. pp. 351–380. doi:10.1007/7854_2016_15. ISBN   978-3-319-52442-9. OCLC   643052237. PMID   27272067.
  4. ↑ Nichols DE, Frescas S, Marona-Lewicka D, Kurrasch-Orbaugh DM (September 2002). "Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of the diethylamide moiety in the potent hallucinogenic agent N,N-diethyllysergamide (LSD)" (PDF). Journal of Medicinal Chemistry. 45 (19): 4344–9. doi:10.1021/jm020153s. PMID   12213075.
  5. ↑ Morris H (1 May 2011). "Life Is a Cosmic Giggle on the Breath of the Universe". Vice Magazine. Retrieved 2011-06-15.
  6. ↑ Cole K (2005). Lysergic. Indianapolis: Dog Ear Publishing. ISBN   978-1598580075.
  7. ↑ LSZ Thread. UKChemicalResearch.org
  8. 1 2 ACMD (10 June 2014). "Update of the Generic Definition for Tryptamines" (PDF). UK Home Office. p. 12. Retrieved 10 June 2014.
  9. ↑ Power M (2014-01-29). "The Drug Revolution That No One Can Stop".
  10. ↑ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Der Bundesrat.
  11. ↑ "Bekendtgørelse om euforiserende stoffer - ni nye stoffer tilføjet" (in Danish). Lægemiddelstyrelsen. 31 August 2015.
  12. ↑ "31 nya ämnen kan klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten. November 2015.
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