LPD-824

{{Short description|Chemical compound}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | Watchedfields = verified | verifiedrevid = 415673871 | image = LPD-824-2d-skeletal.svg | image_class = skin-invert-image | width = 165px | image2 = LPD-824 3D.png | image_class2 = bg-transparent | width2 = 225px

| tradename = | routes_of_administration = | class = Serotonin receptor modulator; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen

| legal_AU = | legal_CA = | legal_UK = | legal_US =

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 2385-87-7 | PubChem = 200628 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 173678 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 302524 | synonyms = LPD-824; LPD824; ''N''-Pyrrolidyllysergamide; Lysergic acid pyrrolidide; LA-Pyr; LSD-Pyr

| IUPAC_name = (8β)-6-Methyl-8-(pyrrolidin-1-ylcarbonyl)-9,10-didehydroergoline | C=20 | H=23 | N=3 | O=1 | SMILES = O=C(N1CCCC1)[C@@H]4C=C3c5cccc2c5c(c[nH]2)C[C@H]3N(C4)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = SETDYMMXQQXCRP-RDTXWAMCSA-N }}

'''''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).<ref name="TiHKAL">{{Cite web | title = Erowid Online Books : "TIHKAL" - #26 LSD-25 | url = https://erowid.org/library/books_online/tihkal/tihkal26.shtml }}</ref><ref name="Parrish_2007">{{cite web | vauthors = Parrish JC | title = Toward a molecular understanding of hallucinogen action | date = 30 October 2007 | website = Purdue e-Pubs | url = https://bitnest.netfirms.com/external/ProQuest/3263617 | quote = 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 [...] }}</ref><ref name="Nichols_2012">{{cite journal | vauthors = Nichols DE | title = Structure–activity relationships of serotonin 5-HT2A agonists | journal = Wiley Interdisciplinary Reviews: Membrane Transport and Signaling | volume = 1 | issue = 5 | pages = 559–579 | date = 2012 | doi = 10.1002/wmts.42 | issn = 2190-460X | doi-access = free | quote = 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. }}</ref><ref name="Dunn_1974">{{cite journal | vauthors = Dunn WJ, Bederka JP | title = The role of hydrophobicity in the antiserotonin activity of LSD analogs | journal = Research Communications in Chemical Pathology and Pharmacology | volume = 7 | issue = 2 | pages = 275–285 | date = February 1974 | pmid = 4818374 }}</ref> It is the analogue of LSD in which the ''N'',''N''-diethylamide moiety has been cyclized into an ''N'',''N''-pyrrolidide ring.<ref name="TiHKAL" /><ref name="Parrish_2007" />

==Use and effects== The drug has been reported to have mild and relatively short-lasting LSD-like effects in humans at an oral dose of 800{{nbsp}}μg equivalent to one-tenth this amount of LSD (i.e., 80{{nbsp}}μg).<ref name="TiHKAL" /><ref name="Fanchamps_1978">{{cite book | vauthors = Fanchamps A | chapter = Some Compounds With Hallucinogenic Activity | title = Ergot Alkaloids and Related Compounds | pages = 567–614 | date = 1978 | doi = 10.1007/978-3-642-66775-6_8 | publisher = Springer Berlin Heidelberg | publication-place = Berlin, Heidelberg | isbn = 978-3-642-66777-0 | chapter-url = http://link.springer.com/10.1007/978-3-642-66775-6_8 | access-date = 3 June 2025 | quote = 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). }}</ref><ref name="Isbell_1959">{{cite journal | vauthors = Isbell H, Miner EJ, Logan CR | title = Relationships of psychotomimetic to anti-serotonin potencies of congeners of lysergic acid diethylamide (LSD-25) | journal = Psychopharmacologia | volume = 1 | pages = 20–28 | date = 1959 | pmid = 14405872 | doi = 10.1007/BF00408108 }}</ref> Based on different clinical studies, it is estimated to be 5 to 10% as potent as LSD in humans.<ref name="Fanchamps_1978" /><ref name="Hoffer_1965" /> Its duration was shorter than that of LSD, lasting around 5{{nbsp}}hours as opposed to 7{{nbsp}}hours in the case of LSD.<ref name="Isbell_1959" /> The drug produced nausea at small doses in humans, which was dose-limiting in terms of evaluating its effects.<ref name="Cerletti_1956a" />

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

==Pharmacology== ===Pharmacodynamics=== 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.<ref name="Parrish_2007" /><ref name="Nichols_2018">{{cite book | vauthors = Nichols DE | chapter = Chemistry and Structure-Activity Relationships of Psychedelics | title = Current Topics in Behavioral Neurosciences | volume = 36 | pages = 1–43 | date = 2018 | pmid = 28401524 | doi = 10.1007/7854_2017_475 | isbn = 978-3-662-55878-2 | url = https://bitnest.netfirms.com/external/10.1007/7854_2017_475 | quote = Table 1 5-HT2A 5-HT2C, and 5-HT1A receptor affinity and functional effects for selected lysergamides [...] Pyrrolidide }}</ref><ref name="Nichols_2012" /><ref name="Dunn_1974" /> It also showed affinities for the serotonin 5-HT2C and 5-HT1A receptors similar to those of LSD.<ref name="Parrish_2007" /><ref name="Nichols_2018" /><ref name="Nichols_2012" />

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.<ref name="Fanchamps_1978" /><ref name="Hoffer_1965">{{cite journal | vauthors = Hoffer A | title = D-Lysergic acid diethylamide (LSD): A review of its present status | journal = Clinical Pharmacology and Therapeutics | volume = 6 | issue = 2 | pages = 183–255 | date = 1965 | pmid = 14288188 | doi = 10.1002/cpt196562183 }}</ref><ref name="Cerletti_1956">{{cite journal | vauthors = Cerletti A, Konzett H | title = Spezifische Hemmung von 5-Oxytryptamin-Effekten durch Lysergsäurediäthylamid und ähnliche Körper | journal = Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie | volume = 228 | issue = 1–2 | date = 1956 | doi = 10.1007/BF00259761 | trans-title = Specific inhibition of serotonin effects by lysergic acid diethylamide and similar compounds | issn = 0028-1298 | url = http://link.springer.com/10.1007/BF00259761 | language = de | access-date = 5 June 2025 | url-access = subscription }}</ref> It is described as a very strong hypotensive agent in animals.<ref name="Cerletti_1956a">{{cite book | vauthors = Cerletti A | veditors = Abramson HA | chapter = Lysergic Acid Diethylamide (LSD) and Related Compounds | title = Neuropharmacology: Transactions of the 2nd Conference, May 25-27, 1955, Princeton, N.J. | location = New York | pages = 9–84 | date = 1956 | publisher = Josiah Macy | url = https://books.google.com/books?id=-4aYzAEACAAJ | chapter-url = https://www.erowid.org/references/texts/show/4092docid3753 | quote = 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. }}</ref> In subsequent rodent drug discrimination tests, LPD-824 fully substituted for LSD, albeit with only about 16 to 25% of the potency.<ref name="Oberlender_1992">{{cite journal | vauthors = Oberlender R, Pfaff RC, Johnson MP, Huang XM, Nichols DE | title = Stereoselective LSD-like activity in d-lysergic acid amides of (R)- and (S)-2-aminobutane | journal = Journal of Medicinal Chemistry | volume = 35 | issue = 2 | pages = 203–211 | date = January 1992 | pmid = 1732537 | doi = 10.1021/jm00080a001 | quote = 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 [...] }}</ref><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 | quote = 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. [...] }}</ref>

==History== LPD-824 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 | url = https://onlinelibrary.wiley.com/doi/10.1002/hlca.19550380207 | access-date = 5 June 2025 | url-access = subscription }}</ref><ref name="Ginzel_1957">{{cite book | vauthors = Ginzel KH | veditors = Garattini S, Ghetti V | chapter = The effect of lysergic acid diethylamide on some autonomic reflex patterns | title = Psychotropic Drugs: Proceedings of the International Symposium on Psychotropic Drugs, Milan, May 9-11, 1957 | pages = 48–54 | date = 1957 | publisher = Elsevier Publishing Company | url = https://books.google.com/books?id=yL9rAAAAMAAJ | chapter-url = https://bibliography.maps.org/resources/download/19304 | archive-url = https://web.archive.org/web/20250605141326/https://bibliography.maps.org/resources/download/19304 | archive-date = 5 June 2025 }}</ref><ref name="Ginzel_1958">{{cite journal | vauthors = Ginzel KH | title = The effect of (+)-lysergic acid diethylamide and other drugs on the carotid sinus reflex | journal = British Journal of Pharmacology and Chemotherapy | volume = 13 | issue = 3 | pages = 250–259 | date = September 1958 | pmid = 13584725 | pmc = 1481775 | doi = 10.1111/j.1476-5381.1958.tb00899.x }}</ref><ref name="Abramson_1960">{{cite journal | vauthors = Abramson HA | title = Lysergic acid diethylamide (LSD-25). XXXI. Comparison by questionnaire of psychotomimetic activity of congeners on normal subjects and drug addicts | journal = The Journal of Mental Science | volume = 106 | issue = 444 | pages = 1120–1123 | date = July 1960 | pmid = 13681136 | doi = 10.1192/bjp.106.444.1120 }}</ref>

==Society and culture== ===Legal status=== ====Canada==== LPD-824 is not a controlled substance in Canada as of 2025.<ref name="CDSA">{{cite web | title=Controlled Drugs and Substances Act | website=Department of Justice Canada | url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html | access-date=19 January 2026}}</ref>

====United States==== LPD-824 is not an explicitly controlled substance in the United States.<ref name="OrangeBook2026">{{citation | title = Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026) | date = January 2026 | publisher = U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division | location = United States | url = https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf}}</ref> However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

==See also== * Substituted lysergamide * Lysergic acid pyrrolinide (LPN) * Lysergic acid morpholide (LSM-775) * Lysergic acid piperidide (LSD-Pip) * Lysergic acid azepane (LA-Azepane) * Lysergic acid 2,4-dimethylazetidide (LA-SS-Az, LSZ)

==References== {{Reflist}}

==External links== * [https://isomerdesign.com/pihkal/explore/5335 LPD-824 - Isomer Design] * [https://www.erowid.org/library/books_online/tihkal/tihkal26.shtml LSD-25 (Discusses LPD-824) - TiHKAL - Erowid] * [https://isomerdesign.com/pihkal/read/tk/26 LSD-25 (Discusses LPD-824) - TiHKAL - Isomer Design]

Category:5-HT2A agonists Category:Psychedelic lysergamides Category:1-Pyrrolidinyl compounds Category:Serotonin receptor modulators