Chemistry:DiPLA

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DiPLA, also known as N,N-diisopropyllysergamide or as lysergic acid diisopropylamide, is a putative serotonergic psychedelic of the lysergamide family related to lysergic acid diethylamide (LSD).[1][2][3][4] It is the analogue of LSD in which the N,N-diethyl groups have been replaced with N,N-diisopropyl groups.[3][2][5]

Use and effects

DiPLA is not known to have been assessed in humans.[3][6]

Interactions

Pharmacology

Pharmacodynamics

In an early study, DiPLA showed 23.2% of the antiserotonergic activity of LSD in the isolated rat uterus and hence was about 4-fold less potent than LSD in this assay.[3][4][7] Subsequently, DIPLA was reported to have an affinity (Ki) for the serotonin 5-HT2A receptor of 9.0 to 20.2 nM, which was about 4- to 9-fold lower than that of LSD (Ki = 4.8 nM).[8][2][5][9] It is an agonist of the serotonin 5-HT2A receptor and also interacts with other receptors such as the serotonin 5-HT1A receptor, the serotonin 5-HT2C receptor, and dopamine receptors.[8][1] DIPLA fully substituted for LSD in rodent drug discrimination tests, suggesting that it could have psychedelic effects in humans.[2][9] Unlike other assessed lysergamides however, DIPLA was much less potent than LSD, about 8-fold so in the drug discrimination test.[5][9]

History

DiPLA was first described in the scientific literature by Albert Hofmann and colleagues by 1955.[10][11] Subsequently, it was studied in more detail by David E. Nichols and colleagues in the 1990s and thereafter.[2][5][9][1]

See also

  • Substituted lysergamide
  • Isopropyllysergamide (IPLA)
  • Methylisopropyllysergamide (MIPLA)
  • Ethylisopropyllysergamide (EIPLA)
  • Lysergic acid dipropylamide
  • Lysergic acid dibutylamide (LBB-66)
  • Lysergic acid propylamide

References

  1. ↑ 1.0 1.1 1.2 "The polypharmacology of psychedelics reveals multiple targets for potential therapeutics". Neuron 113 (19): 3129–3142.e9. July 2025. doi:10.1016/j.neuron.2025.06.012. PMID 40683247. https://www.cell.com/cms/10.1016/j.neuron.2025.06.012/attachment/7d8365fe-51f3-4a28-bf40-9999bec837f6/mmc11.pdf. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 "Lysergamides revisited". NIDA Research Monograph 146: 52–73. 1994. PMID 8742794. https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=57. "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. Although all N-isopropyl homologs have only 25 to 30 percent affinity of LSD for this site, it is interesting to note that the N-methyl-N-isopropyl compound discussed earlier has nearly equal affinity to LSD for the 5-HT2 site labeled with the agonist ligand [ 125I]-R-DOI. This illustrates the importance of determining the relative efficacy of these compounds rather than just receptor affinity. [...] TABLE 6. Radioligand binding data for N-methyl-N-isopropyl lysergamides: [ 3H]-ketanserin displacement (unpublished results).". 
  3. ↑ 3.0 3.1 3.2 3.3 "Stereoselective aspects of hallucinogenic drug action and drug discrimination studies of entactogens". Purdue University. May 1989. https://bitnest.netfirms.com/external/Theses/Oberlender1989#page=49. "Table 2. Relative potency values for lysergic acid amides. [...]" 
  4. ↑ 4.0 4.1 "Comparative study on the serotonin antagonism of amide derivatives of lysergic acid and of ergot alkaloids". The Journal of Pharmacology and Experimental Therapeutics 122 (1): 124–136. January 1958. doi:10.1016/S0022-3565(25)11933-2. PMID 13502837. https://bibliography.maps.org/resources/download/19096. 
  5. ↑ 5.0 5.1 5.2 5.3 "Drug discrimination and receptor binding studies of N-isopropyl lysergamide derivatives". Pharmacology Biochemistry and Behavior 47 (3): 667–673. 1994. doi:10.1016/0091-3057(94)90172-4. PMID 8208787. https://linkinghub.elsevier.com/retrieve/pii/0091305794901724. Retrieved 27 July 2025. 
  6. ↑ "Basic Pharmacology and Effects". Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. 2003. pp. 67–137. ISBN 978-0-12-433951-4. https://web.archive.org/web/20250223164514/https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6. 
  7. ↑ "Lysergic acid diethylamide and related substances". Annals of the New York Academy of Sciences 66 (3): 668–676. March 1957. doi:10.1111/j.1749-6632.1957.tb40756.x. PMID 13425249. Bibcode: 1957NYASA..66..668R. https://bibliography.maps.org/resources/download/17981. "Finally, we have the disubstituted amides of d-lysergic acid: the dimethyl, diethyl. di-isopropyl, and dibutyl amides. They are 3 to 5 times weaker than LSD in their antagonism toward serotonin.". 
  8. ↑ 8.0 8.1 "Chemistry and Structure–Activity Relationships of Psychedelics". Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. 36. Berlin, Heidelberg: Springer Berlin Heidelberg. 2017. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. http://link.springer.com/10.1007/7854_2017_475. Retrieved 27 July 2025. 
  9. ↑ 9.0 9.1 9.2 9.3 "LSD and Its Lysergamide Cousins". The Heffter Review of Psychedelic Research (Heffter Research Institute) 2: 80–87. 2001. ISSN 1534-9640. https://www.heffter.org/wp-content/uploads/2020/04/chap6.pdf. "Table 3. Affinity for 5-HT2A and 5-HT1A receptors and potency in the rat two-lever drug discrimination assay for selected lysergic acid amides. [...]". 
  10. ↑ "Amide der stereoisomeren Lysergsäuren und Dihydro-lysergsäuren. 38. Mitteilung über Mutterkornalkaloide". Helvetica Chimica Acta 38 (2): 421–433. 1955. doi:10.1002/hlca.19550380207. ISSN 0018-019X. Bibcode: 1955HChAc..38..421S. 
  11. ↑ "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. 

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