DiPLA

{{cs1 config|name-list-style=vanc|display-authors=6}} {{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

| legal_status =

| 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 of the lysergamide family related to lysergic acid diethylamide (LSD).<ref name="Jain_2025">{{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 }}</ref><ref name="Pfaff_1994">{{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 }}</ref><ref name="Oberlender_1989" /><ref name="Cerletti_1958">{{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 }}</ref> It is the analogue of LSD in which the ''N'',''N''-diethyl groups have been replaced with ''N'',''N''-diisopropyl groups.<ref name="Oberlender_1989" /><ref name="Pfaff_1994" /><ref name="Huang_1994" />

==Use and effects== DiPLA is not known to have been assessed in humans.<ref name="Oberlender_1989" /><ref name="Shulgin_2003">{{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 }}</ref>

==Interactions== {{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

==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.<ref name="Oberlender_1989">{{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. [...] }}</ref><ref name="Cerletti_1958" /><ref name="Rothlin_1957">{{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. }}</ref> Subsequently, DIPLA was reported to have an affinity (Ki) for the serotonin 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).<ref name="Nichols_2017">{{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 }}</ref><ref name="Pfaff_1994" /><ref name="Huang_1994" /><ref name="Nichols_2001">{{cite journal | vauthors = Nichols DE | title = LSD and Its Lysergamide Cousins | journal = The Heffter Review of Psychedelic Research | volume = 2 | pages = 80–87 | date = 2001 | publisher = 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. [...] }}</ref> 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.<ref name="Nichols_2017" /><ref name="Jain_2025" /> DIPLA fully substituted for LSD in rodent drug discrimination tests, suggesting that it could have psychedelic effects in humans.<ref name="Pfaff_1994" /><ref name="Nichols_2001" /> Unlike other assessed lysergamides however, DIPLA was much less potent than LSD, about 8-fold so in the drug discrimination test.<ref name="Huang_1994">{{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 }}</ref><ref name="Nichols_2001" />

==History== DiPLA was first described in the scientific literature by Albert Hofmann and colleagues by 1955.<ref name="Stoll_1955">{{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 }}</ref><ref name="Hofmann_1959">{{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 }}</ref> Subsequently, it was studied in more detail by David E. Nichols and colleagues in the 1990s and thereafter.<ref name="Pfaff_1994" /><ref name="Huang_1994" /><ref name="Nichols_2001" /><ref name="Jain_2025" />

==References== {{Reflist}}

==External links== * [https://isomerdesign.com/pihkal/explore/5332 DiPLA - Isomer Design]

Category:5-HT2A agonists Category:Carboxamides Category:David E. Nichols Category:Diisopropylamino compounds Category:Dopamine receptor modulators Category:Psychedelic lysergamides Category:Serotonin receptor modulators Category:Indoloquinolines