Main page
Community Hub0 subscribers
Community Hub
Lysergic acid
View on Wikipediafrom Wikipedia
 | |
 | |
| Names | |
|---|---|
| IUPAC name
6-Methyl-9,10-didehydroergoline-8β-carboxylic acid
| |
| Systematic IUPAC name
(5R,8R)-7-Methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxylic acid | |
| Identifiers | |
3D model (JSmol)
|
|
| ChEBI | |
| ChemSpider | |
| ECHA InfoCard | 100.001.302 |
PubChem CID
|
|
| UNII | |
CompTox Dashboard (EPA)
|
|
| |
| |
| Properties | |
| C16H16N2O2 | |
| Molar mass | 268.316 g·mol−1 |
| Melting point | 238 to 240 °C (460 to 464 °F; 511 to 513 K) |
| Acidity (pKa) | pKa1 = 7.80, pKa2 = 3.30 [1] |
| Legal status | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
| |
Lysergic acid, also known as D-lysergic acid and (+)-lysergic acid, is a precursor for a wide range of ergoline alkaloids that are produced by the ergot fungus and found in the seeds of Argyreia nervosa (Hawaiian baby woodrose), and Ipomoea species (morning glories, ololiuhqui, tlitliltzin).
Amides of lysergic acid, lysergamides, are widely used as pharmaceuticals and as psychedelic drugs, e.g. lysergic acid diethylamide (LSD). Lysergic acid is listed as a Table I precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.[3]
The name "lysergic acid" comes from the fact that it is a carboxylic acid, and it was first made by hydrolysis of various ergot alkaloids.[4]
Pharmacology
[edit]Lysergic acid failed to produce LSD-like electroencephalogram (EEG) changes in rabbits.[5]
Chemistry
[edit]Synthesis
[edit]Laboratory
[edit]Lysergic acid is generally produced by hydrolysis[6] of natural lysergamides, but can also be synthesized in the laboratory by a complex total synthesis, for example by Robert Burns Woodward's team in 1956.[7] An enantioselective total synthesis based on a palladium-catalyzed domino cyclization reaction has been described in 2011 by Fujii and Ohno.[8] Lysergic acid monohydrate crystallizes in very thin hexagonal leaflets when recrystallized from water. Lysergic acid monohydrate, when dried (140 °C at 2 mmHg or 270 Pa) forms anhydrous lysergic acid.
Biosynthesis
[edit]The biosynthetic route is based on the alkylation of the amino acid tryptophan with dimethylallyl diphosphate (isoprene derived from 3R-mevalonic acid) giving 4-dimethylallyl-L-tryptophan which is N-methylated with S-adenosyl-L-methionine. Oxidative ring closure followed by decarboxylation, reduction, cyclization, oxidation, and allylic isomerization yields D-(+)-lysergic acid.[4] The biosynthetic pathway has been reconsituted in transgenic baker's yeast.[9]
Isomers
[edit]Lysergic acid is a chiral compound with two stereocenters. The isomer with inverted configuration at carbon atom 8 close to the carboxyl group is called isolysergic acid. Inversion at carbon 5 close to the nitrogen atom leads to L-lysergic acid and L-isolysergic acid, respectively.
Society and culture
[edit]Legal status
[edit]In the United States, Lysergic acid and Lysergic acid amide are Schedule III substances.[10]
See also
[edit]References
[edit]- ^ Brown, H. C.; et al. (1955). Braude, E. A.; Nachod, F. C. (eds.). Determination of Organic Structures by Physical Methods. New York, NY: Academic Press.
- ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-15.
- ^ "List of Precursors and Chemicals Frequently Used in the Illicit Manufacture of Narcotic Drugs and Psychotropic Substances Under International Control" (PDF). International Narcotics Control Board. Archived from the original (PDF) on 2008-02-27.
- ^ a b Schiff, P. L. (Oct 15, 2006). "Ergot and its alkaloids". Am. J. Pharm. Educ. 70 (5): 98. doi:10.5688/aj700598. PMC 1637017. PMID 17149427.
- ^ Siddik ZH, Barnes RD, Dring LG, Smith RL, Williams RT (October 1979). "The fate of lysergic acid DI[14C]ethylamide ([14C]LSD) in the rat, guinea pig and rhesus monkey and of [14C]iso-LSD in rat". Biochemical Pharmacology. 28 (20): 3093–3101. doi:10.1016/0006-2952(79)90618-x. PMID 117811.
EEG studies. Synthetic and biosynthetic metabolites of LSD were injected intravenously into conscious restrained male chinchilla rabbits. With LSD itself, de-ethyl-LSD, 12-hydroxy-LSD, 12-methoxy-LSD, 13-hydroxy-LSD, 13-methoxy-LSD and 13-hydroxy-LSD glucuronide, a persistent alerting EEG trace was seen as indicated by an increase in frequency and decrease in amplitude of the waveform. No changes were observed after administration of lysergic acid, di-LSD-disulphide [10], nor-LSD, 14-hydroxy-LSD-glucuronide, 14-methoxy-LSD, lumi-LSD or the metabolic 2-oxo-LSD. [...] Preliminary studies have indicated that some of the metabolites of LSD, as well as the drug itself. produce an activation of the EEG of the conscious rabbit suggesting they may have central activity. These findings will be published elsewhere.
- ^ Martínková, L.; Kren, V.; Cvak, L.; Ovesná, M.; Prepechalová, I. (Nov 17, 2001). "Hydrolysis of lysergamide to lysergic acid by Rhodococcus equi A4". J. Biotechnol. 84 (1): 63–6. doi:10.1016/s0168-1656(00)00332-1. PMID 11035188.
- ^ Kornfeld, Edmund C.; Fornefeld, E. J.; Kline, G. Bruce; Mann, Marjorie J.; Morrison, Dwight E.; Jones, Reuben G.; Woodward, R. B. (1956). "The Total Synthesis of Lysergic Acid". J. Am. Chem. Soc. 78 (13): 3087–3114. doi:10.1021/ja01594a039.
- ^ Inuki, S.; Iwata, A.; Oishi, S.; Fujii, N.; Ohno, H. (2011). "Enantioselective Total Synthesis of (+)-Lysergic Acid, (+)-Lysergol, and (+)-Isolysergol by Palladium-Catalyzed Domino Cyclization of Allenes Bearing Amino and Bromoindolyl Groups". J. Org. Chem. 76 (7): 2072–2083. doi:10.1021/jo102388e. PMID 21361331.
- ^ Wong, Garrett; Lim, Li Rong; Tan, Yong Quan; Go, Maybelle Kho; Bell, David J.; Freemont, Paul S.; Yew, Wen Shan (2022). "Reconstituting the complete biosynthesis of D-lysergic acid in yeast". Nature Communications. 13 (1): 712. Bibcode:2022NatCo..13..712W. doi:10.1038/s41467-022-28386-6. PMC 8821704. PMID 35132076.
- ^ "Federal Register :: Request Access". www.ecfr.gov. Retrieved 2025-10-04.
Look up lysergic or lysergic acid in Wiktionary, the free dictionary.
Lysergic acid
View on Grokipediafrom Grokipedia
Chemistry
Structure and Properties
Lysergic acid is an ergoline alkaloid characterized by a tetracyclic ring system consisting of a tryptamine-derived indole fused to a quinoline-like structure, featuring a carboxylic acid group at the 8-position, a Δ^{9,10} double bond, and an N-methyl group at position 6. The naturally occurring form has the (5R,8R) configuration at the chiral centers. Its IUPAC name is (6aR,9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxylic acid. The molecular formula is C_{16}H_{16}N_2O_2, and the molar mass is 268.32 g/mol.[1][6] Physically, lysergic acid manifests as a white to off-white crystalline solid. It lacks a defined melting point, decomposing at approximately 240 °C. The compound is amphoteric, exhibiting pK_a values of about 3.3 for the carboxylic acid and 7.0 for the basic nitrogen.[7] Lysergic acid demonstrates low solubility in water (slightly soluble, forming zwitterions that limit dissolution) but increased solubility in acidic or alkaline aqueous media. It dissolves moderately in polar organic solvents such as pyridine, methanol, and chloroform, while being sparingly soluble in non-polar solvents like diethyl ether or benzene. These properties stem from the polar carboxylic and amide functionalities alongside the hydrophobic ergoline core.[8][9]Isomers
Lysergic acid contains two chiral centers at C5 and C8 within its ergoline core, yielding four stereoisomers: D-lysergic acid with (5R,8R) configuration, L-lysergic acid with (5S,8S), D-isolysergic acid with (5R,8S), and L-isolysergic acid with (5S,8R).[10][11] The D-lysergic acid isomer predominates in natural sources, such as ergot alkaloids derived from the fungus Claviceps purpurea, while D-isolysergic acid appears in smaller quantities; the L-enantiomers do not occur naturally and arise primarily from synthetic processes or unintended epimerization.[10][12] Isolysergic acids differ from lysergic acids by epimerization at C8, altering the orientation of the carboxylic acid group relative to the C5 hydrogen from trans to cis, which impacts stability and reactivity; this epimerization equilibrates under basic conditions, such as treatment with barium hydroxide or boiling methanol, favoring the lysergic form.[10][11] Only D-lysergic acid exhibits biological relevance as a precursor to active ergoline derivatives, whereas isolysergic and L-isomers show diminished pharmacological potency or inactivity in receptor binding assays.[13][10]Laboratory Synthesis
Lysergic acid is typically prepared in laboratories via semi-synthetic routes from ergot alkaloids such as ergotamine or ergometrine, which are isolated from the fungus Claviceps purpurea.[12] The most common method involves alkaline hydrolysis to cleave the peptide or amide side chains attached to the ergoline core. Ergotamine tartrate is refluxed with potassium hydroxide (e.g., 4 g KOH per 30 g ergotamine) in a water-ethanol mixture (1:3 ratio, 120 mL total volume) for approximately 2 hours, initially yielding lysergamide as the primary product.[14] Further hydrolysis of lysergamide—achieved chemically via prolonged base treatment or enzymatically using bacteria like Rhodococcus equi or Rhodococcus erythropolis—converts it to lysergic acid, with the reaction mixture acidified to isolate the carboxylic acid.[14] [15] Yields vary but can reach around 50-70% for the lysergamide intermediate, though overall efficiency depends on purification steps to separate iso-lysergic acid byproducts formed via epimerization at C-8.[12] Alternative semi-synthetic approaches include hydrazinolysis of ergotamine, which selectively cleaves the amide bond to produce lysergic acid hydrazide, subsequently converted to the free acid.[15] These methods leverage the natural abundance of ergot alkaloids, making them practical for laboratory-scale production despite regulatory controls on precursors.[16] Total synthesis of lysergic acid, independent of natural precursors, was first achieved in 1956 by Robert B. Woodward and colleagues through a lengthy sequence exceeding 20 steps, establishing the ergoline framework via indole construction and ring closures but with low overall yield (approximately 1.1% in later optimizations).[17] [12] Subsequent routes, such as those via Hendrickson or Szantay intermediates or Heck coupling, refined the process but remained complex due to the tetracyclic structure's stereochemical challenges.[12] Recent advancements include a 2023 report of a concise six-step synthesis of racemic lysergic acid from 4-haloindole and halopyridine derivatives, involving coupling, dearomatization, and cyclization, with a 12% overall yield suitable for structure-activity studies.[18] Enantioselective total syntheses, like a 12-step route to (+)-lysergic acid starting from (R)-4-methoxy-3-penten-2-one (12.7% yield), highlight progress in asymmetric catalysis for accessing the natural D-isomer.[19] These synthetic efforts, while elegant, are primarily academic, as semi-synthetic methods dominate for derivative production like lysergic acid diethylamide due to higher scalability.[12]Natural Occurrence and Biosynthesis
Sources in Nature
Lysergic acid is naturally produced by fungi in the genus Claviceps, particularly Claviceps purpurea and Claviceps paspali, as the core structural element of ergot alkaloids found in sclerotia. These compact, fungal resting structures develop in place of grain kernels on infected host plants, primarily cereal crops like rye (Secale cereale) and other grasses, with alkaloid concentrations ranging from 0.15% to 0.5% by dry weight in C. purpurea sclerotia.[12][20] C. purpurea alkaloids include ergopeptines such as ergotamine, which incorporate D-lysergic acid bound to peptide moieties, while C. paspali yields simpler lysergic acid derivatives suitable for biotechnological extraction.[21][22] Other Claviceps species, including C. fusiformis and tropical variants like C. africana, contribute to ergot alkaloid diversity but often accumulate precursors like elymoclavine rather than completing the pathway to lysergic acid.[23] Fungi outside the Clavicipitaceae, such as certain Aspergillus species, have independently evolved lysergic acid amide production, though full lysergic acid biosynthesis remains characteristic of clavicipitaceous ergot producers.[24] In plants, free lysergic acid is not directly accumulated; instead, derivatives like lysergic acid amide (ergine) occur in seeds of Convolvulaceae species such as Argyreia nervosa (Hawaiian baby woodrose), Ipomoea violacea (morning glory), and Rivea corymbosa, likely due to symbiotic endophytic fungi biosynthesizing the alkaloids. These plant-associated sources contain up to 0.04% ergine by seed weight but require hydrolysis to yield lysergic acid, distinguishing them from primary fungal production sites.[25][26]Biosynthetic Pathway
The biosynthesis of lysergic acid occurs primarily in ergot-producing fungi of the family Clavicipitaceae, such as Claviceps purpurea, and shares initial steps with other ergot alkaloids before diverging toward the lysergic acid branch.[27] The pathway begins with the amino acid L-tryptophan as the primary precursor, which undergoes prenylation with dimethylallyl diphosphate (DMAPP) to form 4-dimethylallyl-L-tryptophan (DMAT), catalyzed by the prenyltransferase enzyme encoded by the dmaW gene.[27] [5] This step establishes the tetracyclic ergoline core characteristic of ergot alkaloids.[27] Subsequent transformations involve N-methylation of DMAT to dimethylallyl-L-abrine by the methyltransferase EasF, followed by oxidative cyclization to chanoclavine-I, mediated by the oxidoreductase EasE, catalase EasC, and short-chain dehydrogenase/reductase EasD, yielding chanoclavine-I aldehyde.[27] [5] The pathway then proceeds to agroclavine through a Pictet-Spengler-like reaction and isomerization, catalyzed by the old yellow enzyme EasA and isomerase EasG.[27] [5] From agroclavine, the route specific to lysergic acid diverges from the festuclavine path (leading to dihydrolysergic acid derivatives) via successive oxidations.[27] The cytochrome P450 monooxygenase CloA performs multiple oxidation steps: agroclavine is oxidized to elymoclavine (a 2-electron oxidation at C-8,9), then to paspalic acid (additional 4-electron oxidation), followed by isomerization to D-lysergic acid, completing the Δ9,10-double bond characteristic of lysergic acid.[27] [5] These late-stage transformations by CloA are rate-limiting and have been confirmed through heterologous expression in yeast (Saccharomyces cerevisiae), where co-expression of dmaW, easF, easC, easE, easD, easA, easG, and cloA enabled de novo production of D-lysergic acid from L-tryptophan supplementation, achieving titers up to 1.7 mg/L in fermenters.[5] Variations in enzyme orthologs across fungal species can influence efficiency, but the core pathway remains conserved in lysergic acid-producing strains.[5] Uncertainties persist in the precise mechanisms of chanoclavine-I formation and the exact electron transfers in CloA-mediated steps, though isotopic labeling and genetic knockouts support the outlined sequence.[27]History
Discovery and Early Research
Lysergic acid was first isolated in 1934 by American chemists Walter A. Jacobs and Lyman C. Craig at the Rockefeller Institute for Medical Research through alkaline hydrolysis of ergot alkaloids extracted from the sclerotia of Claviceps purpurea.[28] They obtained the compound as a common degradation product from mixtures including ergotinine and ergocristine, identifying it as an optically active amino acid with the empirical formula C16H16N2O2, which they named lysergic acid due to its role as the core nucleus of ergot alkaloids.[12] This isolation built on prior work isolating individual ergot alkaloids, such as ergotamine by Arthur Stoll in 1918, but marked the first preparation of the pure tetracyclic ergoline carboxylic acid fragment shared across the alkaloid family.[29] In 1936, Jacobs and Craig proposed the partial structure of lysergic acid, determining it contained a substituted indole nucleus linked to a quinoline-like system, based on degradative reactions including ozonolysis, methylation, and decarboxylation studies that yielded known indole derivatives like skatole.[30] Their work confirmed lysergic acid's chirality with two asymmetric centers and distinguished it from its iso-form, isolysergic acid, which arises as an epimer during hydrolysis. This structural insight facilitated further degradation studies, revealing lysergic acid's resistance to certain acylations and its formation of monobasic salts, properties inconsistent with simpler dicarboxylic structures. Early research post-isolation focused on synthesizing stable derivatives for pharmaceutical applications, driven by ergot's historical use in obstetrics and vascular disorders. At Sandoz Laboratories in Basel, Switzerland, Albert Hofmann, starting in the late 1920s, pursued semisynthetic modifications of lysergic acid to develop circulatory and respiratory stimulants, as the parent acid proved unstable and poorly absorbed.[12] By 1938, Hofmann had prepared over two dozen amides, including lysergic acid diethylamide (LSD), via activation of lysergic acid hydrazide or anhydride intermediates, though initial pharmacological screening yielded unremarkable analeptic effects, prompting temporary shelving of the compounds. These efforts underscored lysergic acid's potential as a scaffold for bioactivity but highlighted challenges in handling its sensitivity to light, heat, and epimerization.[31]Development of Derivatives
In the early 20th century, Sandoz Laboratories pursued the isolation and modification of ergot alkaloids to harness their uterotonic and vasoconstrictive properties for medical use. Arthur Stoll achieved the first pure isolation of ergotamine, a lysergic acid peptide derivative, on August 25, 1918, enabling standardized pharmaceutical preparations like Gynergen for migraine treatment and postpartum hemorrhage control.[32] By the mid-1930s, efforts expanded to simpler lysergic acid amides for potentially superior solubility and activity. The structure of ergonovine (also known as ergobasine), a lysergic acid derivative yielding lysergic acid upon hydrolysis, was elucidated in 1935, facilitating its development as a rapid-acting oxytocic agent for obstetrics.[33] Albert Hofmann, continuing this work at Sandoz, systematically synthesized lysergic acid amides as potential analeptics to stimulate circulation and respiration.[34] On November 16, 1938, Hofmann produced lysergic acid diethylamide (LSD-25), the twenty-fifth compound in his series of diethylamide and related derivatives, via coupling of lysergic acid with diethylamine.[34] Initial pharmacological screening revealed no exceptional circulatory benefits, leading to its archival, though subsequent accidental exposure in 1943 uncovered its profound psychoactive effects and spurred further derivative exploration.[35] These semi-synthetic advancements from ergot-derived lysergic acid laid the groundwork for later ergoline-based drugs, prioritizing empirical potency over natural extracts.[12]Pharmacology
Biochemical Mechanisms
Lysergic acid, as a core ergoline alkaloid, primarily interacts with the serotonergic system by binding to various 5-HT receptor subtypes with notable affinity. It exhibits high binding affinity for the 5-HT1D receptor, competing effectively with agonists such as 5-HT, 5-carboxamidotryptamine, and sumatriptan in radioligand binding assays on human brain tissue.[36] This interaction positions lysergic acid as a ligand capable of modulating Gi/o-coupled signaling pathways associated with 5-HT1D, which typically inhibit adenylyl cyclase activity and reduce cyclic AMP levels, thereby influencing vascular tone and neuronal excitability in regions expressing these receptors. Additionally, lysergic acid acts as an agonist at 5-HT2 receptors, contributing to psychotomimetic-like effects observed in preclinical models, though with substantially lower potency than its amidated derivatives.[37] At 5-HT2 subtypes, particularly 5-HT2A, binding triggers Gq/11-protein-mediated activation of phospholipase C, leading to hydrolysis of phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). This cascade mobilizes intracellular calcium stores and activates protein kinase C, altering downstream signaling in cortical and subcortical neurons. Such mechanisms parallel those of related ergolines but are tempered by lysergic acid's structural polarity, which limits its membrane permeability and central nervous system bioavailability compared to lipophilic analogs. As a nonselective ergoline scaffold, lysergic acid also demonstrates affinity for dopamine and adrenergic receptors, enabling pleiotropic effects on monoaminergic transmission.[38] These interactions can inhibit or facilitate neurotransmitter release depending on receptor subtype and tissue context, contributing to its vasoconstrictive properties akin to other ergot alkaloids. However, direct empirical data on lysergic acid's intrinsic efficacy and downstream phosphorylation events (e.g., ERK activation or β-arrestin recruitment) remain sparse, with most insights extrapolated from derivative studies due to its primary role as a biosynthetic precursor rather than a standalone therapeutic agent.Physiological Effects
Lysergic acid exhibits weak physiological activity in humans, primarily due to its low affinity for serotonin receptors compared to amidated derivatives like LSD. Early human administration studies, involving small doses to schizophrenic patients, reported no significant autonomic or hallucinogenic effects, with observations limited to general inhibition of motor and sensory regulated activities such as tapping speed and flicker-fusion thresholds, without marked changes in vital signs or peripheral symptoms.[39][40] In pharmacological assays, lysergic acid demonstrates minimal excitatory effects on isolated smooth muscle tissues, such as the guinea pig ileum, contrasting with stronger responses from peptide-containing ergot derivatives that induce vasoconstriction and uterine contraction.[41] No documented cases of acute toxicity or overdose from lysergic acid alone exist in human literature, reflecting its poor oral bioavailability and rapid metabolism, which limit systemic exposure.[42] Its physiological impact is thus considered negligible at doses relevant to natural occurrence or synthetic exposure, without the pronounced cardiovascular or thermoregulatory alterations seen in LSD intoxication.Derivatives and Applications
Key Derivatives
Lysergic acid serves as the core structure for numerous ergoline alkaloids, primarily through reactions forming amides or incorporating the moiety into peptides, yielding compounds with diverse pharmacological profiles ranging from hallucinogenic to vasoconstrictive effects.[12] These derivatives are typically semisynthetic, derived from lysergic acid extracted from ergot fungi such as Claviceps purpurea, though total syntheses have been developed.[18] Key examples include simple amides like lysergic acid diethylamide and ergonovine, as well as complex ergopeptines like ergotamine.[33] The most notable derivative is lysergic acid diethylamide (LSD), synthesized in 1938 by Albert Hofmann via activation of lysergic acid (often as its hydrazide or anhydride) followed by coupling with diethylamine, resulting in a potent serotonin receptor agonist with hallucinogenic properties at microgram doses.[3] LSD's structure retains the tetracyclic ergoline core with a diethylamide substitution at the carboxylic acid group, conferring high affinity for 5-HT2A receptors.[12] Its psychoactive effects were serendipitously discovered in 1943 after Hofmann's accidental exposure.[18] Ergonovine (ergometrine), a simple amide derivative, features lysergic acid amidated with 2-amino-1-propanol, and occurs naturally in ergot sclerotia; it acts as an uterotonic agent by stimulating smooth muscle contraction via partial agonism at serotonin and dopamine receptors.[33] First isolated in 1935, it is used clinically to prevent postpartum hemorrhage, with onset within minutes of administration.[2] Doses typically range from 0.2 to 0.5 mg intravenously.[33] Ergotamine, a complex ergopeptine, incorporates lysergic acid linked to a cyclol tripeptide (2-proline-5-valine-phenylalanine), exhibiting vasoconstrictive properties through alpha-adrenergic and serotonin receptor interactions, primarily for acute migraine treatment.[43] Semi-synthesized from ergotamine-rich fungal extracts since the 1920s, it is administered orally or rectally at 1-2 mg doses, often combined with caffeine to enhance absorption.[33] Other significant derivatives include lysergic acid amide (LSA or ergine), a naturally occurring primary amide with milder psychoactive effects found in seeds of plants like Ipomoea purpurea, and semisynthetic analogs like bromocriptine, a D-lysergic acid derivative of ergopeptine ergocryptine modified with a bromo substituent for dopamine D2 receptor selectivity in treating Parkinson's disease and hyperprolactinemia.[33][2] These compounds highlight lysergic acid's versatility, though many carry risks of ergotism-like toxicity due to vasoconstriction.[44]| Derivative | Substitution/Key Feature | Primary Use | Year of Synthesis/Isolation |
|---|---|---|---|
| LSD | Diethylamide | Hallucinogen (research) | 1938[3] |
| Ergonovine | 2-Hydroxypropylamide | Uterotonic | 1935[33] |
| Ergotamine | Ergopeptine peptide | Migraine treatment | 1918 (isolation)[33] |
| Bromocriptine | 2-Bromo-ergocryptine | Dopamine agonist | 1970s semisynthesis[2] |