DiPLA

DiPLA
Clinical data
Other names	DiPLA; N,N-Diisopropyllysergamide; Lysergic acid diisopropylamide
Drug class	Serotonin receptor modulator; Serotonergic psychedelic; Hallucinogen
ATC code	None;
Identifiers
	IUPAC name (6aR,9R)-7-methyl-N,N-di(propan-2-yl)-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide;
PubChem CID	101661198;
Chemical and physical data
Formula	C22H29N3O
Molar mass	351.494 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN1C[C@@H](C=C2[C@H]1Cc1c[nH]c3c1c2ccc3)C(=O)N(C(C)C)C(C)C;
	InChI InChI=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; Key: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).¹²³⁴ It is the analogue of LSD in which the N,N-diethyl groups have been replaced with N,N-diisopropyl groups.³²⁵

Use and effects

DiPLA is not known to have been assessed in humans.³⁶

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.³⁴⁷ Subsequently, DIPLA was reported to have an affinity (K_i) for the serotonin 5-HT_2A receptor of 9.0 to 20.2 nM, which was about 4- to 9-fold lower than that of LSD (K_i = 4.8 nM).⁸²⁵⁹ It is an agonist of the serotonin 5-HT_2A receptor and also interacts with other receptors such as the serotonin 5-HT_1A receptor, the serotonin 5-HT_2C receptor, and dopamine receptors.⁸¹ DIPLA fully substituted for LSD in rodent drug discrimination tests, suggesting that it could have psychedelic effects in humans.²⁹ Unlike other assessed lysergamides however, DIPLA was much less potent than LSD, about 8-fold so in the drug discrimination test.⁵⁹

History

DiPLA was first described in the scientific literature by Albert Hofmann and colleagues by 1955.¹⁰¹¹ Subsequently, it was studied in more detail by David E. Nichols and colleagues in the 1990s and thereafter.²⁵⁹¹

References

Jain MK, Gumpper RH, Slocum ST, Schmitz GP, Madsen JS, Tummino TA, et al. (July 2025). "The polypharmacology of psychedelics reveals multiple targets for potential therapeutics" (PDF). Neuron. 113 (19): 3129–3142.e9. doi:10.1016/j.neuron.2025.06.012. PMID 40683247.
Pfaff RC, Huang X, Marona-Lewicka D, Oberlender R, Nichols DE (1994). "Lysergamides revisited" (PDF). NIDA Research Monograph. 146: 52–73. PMID 8742794. Archived from the original (PDF) on 2023-08-05. Retrieved 2025-07-27. 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).
Oberlender RA (May 1989). "Stereoselective aspects of hallucinogenic drug action and drug discrimination studies of entactogens". Purdue e-Pubs. Purdue University. Table 2. Relative potency values for lysergic acid amides. [...]
Cerletti A, Doepfner W (January 1958). "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. doi:10.1016/S0022-3565(25)11933-2. PMID 13502837. Archived from the original on 2025-06-30.
Huang X, Marona-Lewicka D, Pfaff RC, Nichols DE (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. Retrieved 27 July 2025.
Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN 978-0-12-433951-4.
Rothlin E (March 1957). "Lysergic acid diethylamide and related substances". Annals of the New York Academy of Sciences. 66 (3): 668–676. Bibcode:1957NYASA..66..668R. doi:10.1111/j.1749-6632.1957.tb40756.x. PMID 13425249. Archived from the original on 12 July 2025. 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.
Nichols DE (2017). "Chemistry and Structure–Activity Relationships of Psychedelics". Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. Vol. 36. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524. Retrieved 27 July 2025.
Nichols DE (2001). "LSD and Its Lysergamide Cousins" (PDF). The Heffter Review of Psychedelic Research. 2. Heffter Research Institute: 80–87. ISSN 1534-9640. 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. [...]
Stoll A, Hofmann A (1955). "Amide der stereoisomeren Lysergsäuren und Dihydro-lysergsäuren. 38. Mitteilung über Mutterkornalkaloide" [Amides of stereoisomeric lysergic and dihydrolysergic acids. 38. Ergot alkaloids]. Helvetica Chimica Acta. 38 (2): 421–433. Bibcode:1955HChAc..38..421S. doi:10.1002/hlca.19550380207. ISSN 0018-019X.
Hofmann A (June 1959). "Psychotomimetic Drugs: Chemical and Pharmacological Aspects" (PDF). Acta Physiologica et Pharmacologica Neerlandica. 8: 240–258. PMID 13852489.

External links

DiPLA - Isomer Design

[Jain_2025-1] Jain MK, Gumpper RH, Slocum ST, Schmitz GP, Madsen JS, Tummino TA, et al. (July 2025). "The polypharmacology of psychedelics reveals multiple targets for potential therapeutics" (PDF). Neuron. 113 (19): 3129–3142.e9. doi:10.1016/j.neuron.2025.06.012. PMID 40683247.

[Pfaff_1994-2] Pfaff RC, Huang X, Marona-Lewicka D, Oberlender R, Nichols DE (1994). "Lysergamides revisited" (PDF). NIDA Research Monograph. 146: 52–73. PMID 8742794. Archived from the original (PDF) on 2023-08-05. Retrieved 2025-07-27. 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).

[Oberlender_1989-3] Oberlender RA (May 1989). "Stereoselective aspects of hallucinogenic drug action and drug discrimination studies of entactogens". Purdue e-Pubs. Purdue University. Table 2. Relative potency values for lysergic acid amides. [...]

[Cerletti_1958-4] Cerletti A, Doepfner W (January 1958). "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. doi:10.1016/S0022-3565(25)11933-2. PMID 13502837. Archived from the original on 2025-06-30.

[Huang_1994-5] Huang X, Marona-Lewicka D, Pfaff RC, Nichols DE (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. Retrieved 27 July 2025.

[Shulgin_2003-6] Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN 978-0-12-433951-4.

[Rothlin_1957-7] Rothlin E (March 1957). "Lysergic acid diethylamide and related substances". Annals of the New York Academy of Sciences. 66 (3): 668–676. Bibcode:1957NYASA..66..668R. doi:10.1111/j.1749-6632.1957.tb40756.x. PMID 13425249. Archived from the original on 12 July 2025. 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.

[Nichols_2017-8] Nichols DE (2017). "Chemistry and Structure–Activity Relationships of Psychedelics". Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. Vol. 36. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524. Retrieved 27 July 2025.

[Nichols_2001-9] Nichols DE (2001). "LSD and Its Lysergamide Cousins" (PDF). The Heffter Review of Psychedelic Research. 2. Heffter Research Institute: 80–87. ISSN 1534-9640. 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. [...]

[Stoll_1955-10] Stoll A, Hofmann A (1955). "Amide der stereoisomeren Lysergsäuren und Dihydro-lysergsäuren. 38. Mitteilung über Mutterkornalkaloide" [Amides of stereoisomeric lysergic and dihydrolysergic acids. 38. Ergot alkaloids]. Helvetica Chimica Acta. 38 (2): 421–433. Bibcode:1955HChAc..38..421S. doi:10.1002/hlca.19550380207. ISSN 0018-019X.

[Hofmann_1959-11] Hofmann A (June 1959). "Psychotomimetic Drugs: Chemical and Pharmacological Aspects" (PDF). Acta Physiologica et Pharmacologica Neerlandica. 8: 240–258. PMID 13852489.

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