# DiPLA
> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/DiPLA
> Markdown URL: https://mediated.wiki/source/DiPLA.md
> Source: https://en.wikipedia.org/wiki/DiPLA
> Source revision: 1338630939
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)
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{{Infobox drug
| drug_name =
| image = N,N-Diisopropyllysergamide.svg
| image_class = skin-invert-image
| width = 185px
| image2 = DiPLA 3D.png
| image_class2 = bg-transparent
| width2 = 235px
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| class = [Serotonin receptor modulator](/source/Serotonin_receptor_modulator); [Serotonergic psychedelic](/source/Serotonergic_psychedelic); [Hallucinogen](/source/Hallucinogen)
| ATC_prefix = None
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| PubChem = 101661198
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| synonyms = DiPLA; ''N'',''N''-Diisopropyllysergamide; Lysergic acid diisopropylamide
| IUPAC_name = (6a''R'',9''R'')-7-methyl-''N'',''N''-di(propan-2-yl)-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide
| C=22 | H=29 | N=3 | O=1
| SMILES = CN1C[C@@H](C=C2[C@H]1Cc1c[nH]c3c1c2ccc3)C(=O)N(C(C)C)C(C)C
| StdInChI = 1S/C22H29N3O/c1-13(2)25(14(3)4)22(26)16-9-18-17-7-6-8-19-21(17)15(11-23-19)10-20(18)24(5)12-16/h6-9,11,13-14,16,20,23H,10,12H2,1-5H3/t16-,20-/m1/s1
| StdInChIKey = UGLFFFFNSMDCNO-OXQOHEQNSA-N
}}
'''DiPLA''', also known as '''''N'',''N''-diisopropyllysergamide''' or as '''lysergic acid diisopropylamide''', is a putative [serotonergic psychedelic](/source/serotonergic_psychedelic) of the [lysergamide](/source/substituted_lysergamide) family related to [lysergic acid diethylamide](/source/lysergic_acid_diethylamide) (LSD).[{{cite journal | vauthors = Jain MK, Gumpper RH, Slocum ST, Schmitz GP, Madsen JS, Tummino TA, Suomivuori CM, Huang XP, Shub L, DiBerto JF, Kim K, DeLeon C, Krumm BE, Fay JF, Keiser M, Hauser AS, Dror RO, Shoichet B, Gloriam DE, Nichols DE, Roth BL | title = The polypharmacology of psychedelics reveals multiple targets for potential therapeutics | journal = Neuron | date = July 2025 | volume = 113 | issue = 19 | pages = 3129–3142.e9 | pmid = 40683247 | doi = 10.1016/j.neuron.2025.06.012 | url = https://www.cell.com/cms/10.1016/j.neuron.2025.06.012/attachment/7d8365fe-51f3-4a28-bf40-9999bec837f6/mmc11.pdf }}][{{cite journal | vauthors = Pfaff RC, Huang X, Marona-Lewicka D, Oberlender R, Nichols DE | title = Lysergamides revisited | journal = NIDA Research Monograph | volume = 146 | pages = 52–73 | date = 1994 | pmid = 8742794 | url = https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=57 | quote = 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). | archive-date = 2023-08-05 | access-date = 2025-07-27 | archive-url = https://web.archive.org/web/20230805004551/https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=57 | url-status = dead }}][{{cite journal | vauthors = Cerletti A, Doepfner W | title = Comparative study on the serotonin antagonism of amide derivatives of lysergic acid and of ergot alkaloids | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 122 | issue = 1 | pages = 124–136 | date = January 1958 | pmid = 13502837 | doi = 10.1016/S0022-3565(25)11933-2 | url = https://bibliography.maps.org/resources/download/19096 | archive-url = https://web.archive.org/web/20250630233202/https://bibliography.maps.org/resources/download/19096 | archive-date = 2025-06-30 }}] It is the [analogue](/source/structural_analog) of LSD in which the ''N'',''N''-di[ethyl group](/source/ethyl_group)s have been replaced with ''N'',''N''-di[isopropyl group](/source/isopropyl_group)s.[{{cite book | vauthors = Shulgin AT | veditors = Laing RR | chapter = Basic Pharmacology and Effects | title = Hallucinogens: A Forensic Drug Handbook | pages = 67–137 | year = 2003 | publisher = Elsevier Science | series = Forensic Drug Handbook Series | isbn = 978-0-12-433951-4 | url = https://books.google.com/books?id=l1DrqgobbcwC | chapter-url = https://web.archive.org/web/20250223164514/https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6 }}]
==Interactions==
{{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}
==Pharmacology==
===Pharmacodynamics===
In an early study, DiPLA showed 23.2% of the [antiserotonergic](/source/antiserotonergic) activity of LSD in the isolated rat [uterus](/source/uterus) and hence was about 4-fold less [potent](/source/potency_(pharmacology)) than LSD in this [assay](/source/bioassay).[{{cite web | vauthors = Oberlender RA | title = Stereoselective aspects of hallucinogenic drug action and drug discrimination studies of entactogens | date = May 1989 | publisher = Purdue University | website = Purdue e-Pubs | url = https://bitnest.netfirms.com/external/Theses/Oberlender1989#page=49 | quote = Table 2. Relative potency values for lysergic acid amides. [...] }}][{{cite journal | vauthors = Rothlin E | title = Lysergic acid diethylamide and related substances | journal = Annals of the New York Academy of Sciences | volume = 66 | issue = 3 | pages = 668–676 | date = March 1957 | pmid = 13425249 | doi = 10.1111/j.1749-6632.1957.tb40756.x | bibcode = 1957NYASA..66..668R | url = https://bibliography.maps.org/resources/download/17981 | archive-url = https://web.archive.org/web/20250712025029/https://bibliography.maps.org/resources/download/17981 | archive-date = 12 July 2025 | quote = 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. }}] Subsequently, DIPLA was reported to have an [affinity](/source/affinity_(pharmacology)) (Ki) for the [serotonin](/source/serotonin) [5-HT2A receptor](/source/5-HT2A_receptor) of 9.0 to 20.2{{nbsp}}nM, which was about 4- to 9-fold lower than that of LSD (Ki = 4.8{{nbsp}}nM).[{{cite book | vauthors = Nichols DE | chapter = Chemistry and Structure–Activity Relationships of Psychedelics | title = Behavioral Neurobiology of Psychedelic Drugs | volume = 36 | pages = 1–43 | date = 2017 | pmid = 28401524 | doi = 10.1007/7854_2017_475 | series = Current Topics in Behavioral Neurosciences | publisher = Springer Berlin Heidelberg | publication-place = Berlin, Heidelberg | isbn = 978-3-662-55878-2 | url = http://link.springer.com/10.1007/7854_2017_475 | access-date = 27 July 2025 }}][{{cite journal | vauthors = [Nichols DE](/source/David_E._Nichols) | title = LSD and Its Lysergamide Cousins | journal = The Heffter Review of Psychedelic Research | volume = 2 | pages = 80–87 | date = 2001 | publisher = [Heffter Research Institute](/source/Heffter_Research_Institute) | issn = 1534-9640 | url = https://www.heffter.org/wp-content/uploads/2020/04/chap6.pdf | quote = 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. [...] }}] It is an [agonist](/source/agonist) of the serotonin 5-HT2A receptor and also interacts with other receptors such as the serotonin [5-HT1A receptor](/source/5-HT1A_receptor), the serotonin [5-HT2C receptor](/source/5-HT2C_receptor), and [dopamine receptor](/source/dopamine_receptor)s.[{{cite journal | vauthors = Huang X, Marona-Lewicka D, Pfaff RC, Nichols DE | title = Drug discrimination and receptor binding studies of N-isopropyl lysergamide derivatives | journal = Pharmacology Biochemistry and Behavior | volume = 47 | issue = 3 | pages = 667–673 | date = 1994 | pmid = 8208787 | doi = 10.1016/0091-3057(94)90172-4 | url = https://linkinghub.elsevier.com/retrieve/pii/0091305794901724 | access-date = 27 July 2025 | url-access = subscription }}][{{cite journal | vauthors = Stoll A, Hofmann A | title = Amide der stereoisomeren Lysergsäuren und Dihydro-lysergsäuren. 38. Mitteilung über Mutterkornalkaloide | journal = Helvetica Chimica Acta | volume = 38 | issue = 2 | pages = 421–433 | date = 1955 | doi = 10.1002/hlca.19550380207 | bibcode = 1955HChAc..38..421S | trans-title = Amides of stereoisomeric lysergic and dihydrolysergic acids. 38. Ergot alkaloids | issn = 0018-019X }}][{{cite journal | vauthors = Hofmann A | title = Psychotomimetic Drugs: Chemical and Pharmacological Aspects | journal = Acta Physiologica et Pharmacologica Neerlandica | volume = 8 | pages = 240–258 | date = June 1959 | pmid = 13852489 | url = https://www.samorini.it/doc1/alt_aut/ek/hofmann-psychotomimetic-drugs.pdf }}] Subsequently, it was studied in more detail by [David E. Nichols](/source/David_E._Nichols) and colleagues in the 1990s and thereafter.