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LPD-824

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LPD-824
A chemical diagram of LPD-824
Clinical data
Other namesLPD-824; LPD824; N-Pyrrolidyllysergamide; Lysergic acid pyrrolidide; LA-Pyr; LSD-Pyr
Drug classSerotonin receptor modulator; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
Identifiers
  • (8β)-6-Methyl-8-(pyrrolidin-1-ylcarbonyl)-9,10-didehydroergoline
CAS Number
PubChem CID
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC20H23N3O
Molar mass321.424 g·mol−1
3D model (JSmol)
  • O=C(N1CCCC1)[C@@H]4C=C3c5cccc2c5c(c[nH]2)C[C@H]3N(C4)C
  • InChI=1S/C20H23N3O/c1-22-12-14(20(24)23-7-2-3-8-23)9-16-15-5-4-6-17-19(15)13(11-21-17)10-18(16)22/h4-6,9,11,14,18,21H,2-3,7-8,10,12H2,1H3/t14-,18-/m1/s1 checkY
  • Key:SETDYMMXQQXCRP-RDTXWAMCSA-N checkY
  (verify)

N-Pyrrolidyllysergamide (LPD-824), also known as lysergic acid pyrrolidide (LA-Pyr), is a psychedelic drug 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-diethylamide moiety has been cyclized into an N,N-pyrrolidide ring.[1][2]

Use and effects

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The drug has been reported to have mild and relatively short-lasting LSD-like effects in humans at an oral dose of 800 μg equivalent to one-tenth this amount of LSD (i.e., 80 μg).[1][5][6] Based on different clinical studies, it is estimated to be 5 to 10% as potent as LSD in humans.[5][7] Its duration was shorter than that of LSD, lasting around 5 hours as opposed to 7 hours in the case of LSD.[6] The drug produced nausea at small doses in humans, which was dose-limiting in terms of evaluating its effects.[8]

Pharmacology

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LPD-824 is known to be a serotonin receptor modulator, including of the serotonin 5-HT2A receptor, where it acted as a partial agonist with about 17-fold lower potency than LSD but an efficacy slightly higher than that of LSD in terms of phosphatidylinositol (PI) hydrolysis.[2][9][3][4] It also showed affinities for the serotonin 5-HT2C and 5-HT1A receptors similar to those of LSD.[2][9][3]

It had about 5 to 10% of the potency of LSD in preclinical studies with animals, for instance in terms of serotonin antagonism in the rat uterus and hyperthermia in rabbits.[5][7][10] It is described as a very strong hypotensive agent in animals.[8] In subsequent rodent drug discrimination tests, LPD-824 fully substituted for LSD, albeit with only about 16 to 25% of the potency.[11][12]

History

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LPD-824 was first described in the scientific literature by Albert Hofmann and colleagues by 1955.[13][14][15][16]

See also

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References

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  1. ^ a b c "Erowid Online Books : "TIHKAL" - #26 LSD-25".
  2. ^ a b c d Parrish JC (30 October 2007). "Toward a molecular understanding of hallucinogen action". Purdue e-Pubs. Figure A.1 The series of amide substituted LSD derivatives used in this study. [...] LA-Pyr [...] Table A.1 Results of competition binding experiments and IP accumulation assays for the series of ergolines illustrated in Figure A.1. [...] LA-Pyr [...]
  3. ^ a b c Nichols DE (2012). "Structure–activity relationships of serotonin 5-HT2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi:10.1002/wmts.42. ISSN 2190-460X. TABLE 1 5-HT2A Receptor Affinity and Functional Effects of Selected Lysergamides1 [...] 1 Data from Parrish.42. [...] 42. Parrish JC. Toward a molecular understanding of hallucinogen action. 2006. Purdue University.
  4. ^ a b Dunn WJ, Bederka JP (February 1974). "The role of hydrophobicity in the antiserotonin activity of LSD analogs". Research Communications in Chemical Pathology and Pharmacology. 7 (2): 275–285. PMID 4818374.
  5. ^ a b c Fanchamps A (1978). "Some Compounds With Hallucinogenic Activity". Ergot Alkaloids and Related Compounds. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 567–614. doi:10.1007/978-3-642-66775-6_8. ISBN 978-3-642-66777-0. Retrieved 3 June 2025. Lysergic acid pyrrolidide (LPD 824, No. 73 f) exhibits a modest LSD-like psychic effect (MURPHREE et a!., 1958), which ABRAMSON (1959) quantifies at 5% and ISBELL et a!. (1959 a) at 10% of the LSD-activity. As a serotonin-inhibitor, it shows 5% of the LSD-potency (CERLETTI and DOEPFNER, 1958a). Its dual action on the body temperature of the rat is identical to that of LSD (CERLETTI, 1956); as a pyretogenic in the rabbit, it exhibits 10% of the LSD potency (Sandoz Res. Lab., 1958).
  6. ^ a b Isbell H, Miner EJ, Logan CR (1959). "Relationships of psychotomimetic to anti-serotonin potencies of congeners of lysergic acid diethylamide (LSD-25)". Psychopharmacologia. 1: 20–28. doi:10.1007/BF00408108. PMID 14405872.
  7. ^ a b Hoffer A (1965). "D-Lysergic acid diethylamide (LSD): A review of its present status". Clinical Pharmacology and Therapeutics. 6 (2): 183–255. doi:10.1002/cpt196562183. PMID 14288188.
  8. ^ a b Cerletti A (1956). "Lysergic Acid Diethylamide (LSD) and Related Compounds". In Abramson HA (ed.). Neuropharmacology: Transactions of the 2nd Conference, May 25-27, 1955, Princeton, N.J. New York: Josiah Macy. pp. 9–84. Cerletti: LPD-824 is chemically related to LSD. It is the pyrrolidid of lysergic acid, having the diethylamino group closed to a pyrrolidine nucleus (Figure 7). When this substance was tested in man, doses up to 1/2 μg./kg, were given intravenously without producing any LSD-like symptoms. Pharmacologically LPD is a very strong hypotensive agent. In animals 10 μg./kg. produces hypotension, both in cats and in dogs. As already said, in human subjects it had no psychic effect, but produced nausea in such small doses that a hypotensive effect could not be achieved.
  9. ^ a b Nichols DE (2018). "Chemistry and Structure-Activity Relationships of Psychedelics". Current Topics in Behavioral Neurosciences. Vol. 36. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524. Table 1 5-HT2A 5-HT2C, and 5-HT1A receptor affinity and functional effects for selected lysergamides [...] Pyrrolidide
  10. ^ Cerletti A, Konzett H (1956). "Spezifische Hemmung von 5-Oxytryptamin-Effekten durch Lysergsäurediäthylamid und ähnliche Körper" [Specific inhibition of serotonin effects by lysergic acid diethylamide and similar compounds]. Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie (in German). 228 (1–2). doi:10.1007/BF00259761. ISSN 0028-1298. Retrieved 5 June 2025.
  11. ^ Oberlender R, Pfaff RC, Johnson MP, Huang XM, Nichols DE (January 1992). "Stereoselective LSD-like activity in d-lysergic acid amides of (R)- and (S)-2-aminobutane". Journal of Medicinal Chemistry. 35 (2): 203–211. doi:10.1021/jm00080a001. PMID 1732537. The pyrrolidyl amide (4) was also included in the behavioral pharmacology part of this study, [...] Table I. Potency of Lysergic Acid Amides in 1-Trained Rats [...]
  12. ^ Oberlender RA (May 1989). "Stereoselective aspects of hallucinogenic drug action and drug discrimination studies of entactogens". Purdue e-Pubs. Purdue University. The results of the drug discrimination testing are given in Table 3. The experimental data can be found in Table 15 in appendix B. The four isomers of 17, and the pyrrolidide 5, completely substituted for LSD. [...] Table 3. Potency of lysergic acid amides in LSD-trained rats. [...]
  13. ^ 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. doi:10.1002/hlca.19550380207. ISSN 0018-019X. Retrieved 5 June 2025.
  14. ^ Ginzel KH (1957). "The effect of lysergic acid diethylamide on some autonomic reflex patterns". In Garattini S, Ghetti V (eds.). Psychotropic Drugs: Proceedings of the International Symposium on Psychotropic Drugs, Milan, May 9-11, 1957. Elsevier Publishing Company. pp. 48–54. Archived from the original on 5 June 2025.
  15. ^ Ginzel KH (September 1958). "The effect of (+)-lysergic acid diethylamide and other drugs on the carotid sinus reflex". British Journal of Pharmacology and Chemotherapy. 13 (3): 250–259. doi:10.1111/j.1476-5381.1958.tb00899.x. PMC 1481775. PMID 13584725.
  16. ^ Abramson HA (July 1960). "Lysergic acid diethylamide (LSD-25). XXXI. Comparison by questionnaire of psychotomimetic activity of congeners on normal subjects and drug addicts". The Journal of Mental Science. 106 (444): 1120–1123. doi:10.1192/bjp.106.444.1120. PMID 13681136.
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