Lysergamides, also known as ergoamides  2.5 Lysergic acid and LSD, page 6970 Results and discussion § Biosynthetic resolution of the ergot alkaloid pathway RESULTS AND DISCUSSION, page 7141 or as lysergic acid amides, are amides of lysergic acid (LA). They are ergolines, with some lysergamides being found naturally in ergot as well as other fungi. Lysergamides are notable in containing embedded phenethylamine and tryptamine moieties within their ergoline ring system.

The simplest lysergamides are ergine (lysergic acid amide; LSA) and isoergine (iso-lysergic acid amide; iso-LSA). In terms of pharmacology, the lysergamides include numerous serotonin and dopamine receptor agonists, most notably the psychedelic drug lysergic acid diethylamide (LSD) but also a number of pharmaceutical drugs like ergometrine, methylergometrine, methysergide, and cabergoline. Various analogues of LSD, such as the psychedelics ALD-52 (1A-LSD), ETH-LAD, LSZ, and 1P-LSD and the non-hallucinogenic 2-bromo-LSD (BOL-148), have also been developed. Ergopeptines like ergotamine, dihydroergotamine, and bromocriptine are also lysergamides, but with addition of a small peptide moiety at the amide. Close analogues of lysergamides that are not technically lysergamides themselves include lisuride, terguride, bromerguride, and JRT.

Lysergamides were first discovered and described in the 1930s.

Simplified or partial ergolines and lysergamides, such as NDTDI (8,10-seco-LSD), UCD0120, and N-DEAOP-NMT, are also known.

Use and effects The doses, potencies, durations, and effects of lysergamides have been reviewed by Alexander Shulgin. They have also been reviewed by Albert Hofmann, David E. Nichols, and other researchers.

+ Doses, potencies, and durations of LSD and its analogues Common name Code Dose Potency (×LSD) Duration Lysergic acid amide (LSA; ergine) LA-111 500–6,000 μg ≤10% ~4–10 hours Isolysergic acid amide (iso-LSA; isoergine) Iso-LA-819 2,000–5,000 μg <10% ~4–10 hours Lysergic acid methylamide LAM ~500 μg ≤20% Unknown Lysergic acid dimethylamide DAM-57 500–1,200 μg 10% Unknown Lysergic acid ethylamide (LAE) LAE-32 500–1,600 μg ≤10% Unknown 1-Acetyl-LAE ALA-10, 1A-LAE ~1,200 μg ≤10% Unknown 1-Methyl-LAE MLA-74 ~2,000 μg 5% Unknown Lysergic acid methylethylamide LME-54 Unknown ~33% Unknown Lysergic acid diethylamide (LSD) LSD-25, METH-LAD 50–200 μg 100% 8–12 hours Isolysergic acid diethylamide Iso-LSD >4,000 μg <2% Unknown l-Lysergic acid diethylamide l-LSD >10,000 μg <1% Unknown l-Isolysergic acid diethylamide l-Iso-LSD >500 μg <5% Unknown 2,3-Dihydro-LSD 2,3-DH-LSD ~150–400 μg ~15% ~8–12 hours 9,10-Dihydro-LSD 9,10-DH-LSD >2,500 μg <2% Unknown 10-Hydroxy-9,10-dihydro-LSD Lumi-LSD Unknown <1% Unknown 2-Bromo-LSD BOL-148 >1,000 μg (≥6,000 μg) <10% (≤2%) Unknown 2-Iodo-LSD IOL Unknown Unknown Unknown 2-Oxo-LSD (2-oxy-LSD) – >300 μg Unknown Unknown 1-Acetyl-LSD ALD-52, 1A-LSD 100–200 μg 100% ~8–12 hours 1-Methyl-LSD MLD-41 200–300 μg 30% Unknown 1-Hydroxymethyl-LSD OML-632 Unknown ~70% Unknown 1-Propionyl-LSD 1P-LSD 100–200 μg 100% ~8–12 hours 1-Methyl-2-bromo-LSD MBL-61, MOB-61 >10,000 μg <1% Unknown 1-Methyl-2-iodo-LSD MIL Unknown Unknown Unknown Lysergic acid propylamide LAP >500 μg <20% Unknown Lysergic acid methylpropylamide LMP-55; LAMPA; MPLA >100 μg <100% Unknown Lysergic acid ethylpropylamide LEP-57; EPLA Unknown ~33% Unknown Lysergic acid methylisopropylamide MiPLA 180–300 μg ~33–50% Unknown Lysergic acid dipropylamide DPL >1,000 μg <10% Unknown Lysergic acid dibutylamide LBB-66 Unknown 0% Unknown Lysergic acid diallylamide DAL >1,000 μg <10% Unknown Ergonovine (ergometrine)a – 5,000–10,000 μg ≤1% Unknown Methylergonovine (methylergometrine)b – 2,000 μg 5% Unknown Propisergidec PML-946 >3,000 μg Unknown Unknown Methysergided UML-491 4,000–8,000 μg 2% Unknown Lysergic acid piperidide LA-Pip Unknown Unknown Unknown Lysergic acid pyrrolidide (LPD) LPD-824 ~800 μg 5–10% Unknown Lysergic acid pyrrolinide LPN Unknown Unknown Unknown 1-Methyl-LPD MPD-75 >1,600 μg ≤10% Unknown Lysergic acid morpholide LSM-775, SLM 300–600 μg 10–30% Unknown Lysergic acid 2,4-dimethylazetidide LA-SS-Az, LSZ 100–300 μg 50% ~4–10 hours Nor-LSD (6-nor-LSD) H-LAD >500 μg <20% Unknown 6-Ethyl-nor-LSD ETH-LAD 40–150 μg 200% 8–12 hours 6-Propyl-nor-LSD PRO-LAD 80–200 μg 100% 6–8 hours 6-Allyl-nor-LSD AL-LAD, ALLY-LAD 50–160 μg 100% 6–8 hours 6-n-Butyl-nor-LSD BU-LAD ≥400–500 μg <30% Unknown 6-Propynyl-nor-LSD PARGY-LAD 160–500 μg 20–60% Unknown 6-(β-Phenethyl)-nor-LSD PHENETH-LAD >350–500 μg <30% Unknown Footnotes: a = Ergonovine is lysergic acid hydroxyisopropylamide. b = Methylergonovine is lysergic acid hydroxy-sec-butylamide. c = Propisergide is 1-methylergonovine. d = Methysergide is 1-methylmethylergonovine. Refs: Main: Additional:

The properties of various additional lysergamides, for instance in terms of serotonin antagonism, have also been described.

Interactions

Pharmacology Pharmacodynamics

+ Compound 5-HT1A 5-HT1B 5-HT1D 5-HT1E 5-HT2A 5-HT2B 5-HT2C 5-HT3 5-HT5A 5-HT6 5-HT7 D1 D2 D3 D4 D5 LSD 5.9 21 3.5 135 8.5 5.5 17 – 1.8 16 8.5 288 204 37 112 955 DAM-57 14 18 17 56 12 16 87 – 42 19 23 676 – 309 955 2,000 DiPLA 58 89 25 457 15 17 234 – 17 49 26 135 234 25 219 316 LAMPA 13 27 6.6 – 11 4.9 58 – 19 35 6.5 339 204 35 32 794 LSZ 2.3 63 18 224 16 3.5 15 – 32 18 35 468 115 9.1 129 1,150 NorLSD 7.8 141 37 407 15 54 525 – 100 14 51 – – 76 275 – ETH-LAD 3.5 32 15 85 9.3 18 56 – 21 21 11 417 158 81 240 891 AL-LAD 6.0 275 78 479 17 14 68 – 11 50 42 – 269 27 155 – MAL-LAD 174 – 295 – 28 54 479 – 89 1,050 200 – – 363 3,240 – BU-LAD 21 2,190 129 1,350 21 16 25 – 91 26 123 417 813 91 661 3,630 Lisuride 4.1 63 13 93 25 16 50 – 5.6 18 9.5 174 10 5.6 10 1,050

+ Compound 5-HT1A 5-HT1B 5-HT1D 5-HT1E 5-HT2A 5-HT2B 5-HT2C 5-HT3 5-HT5A 5-HT6 5-HT7 D1 D2 D3 D4 D5 LSD 7.3 3.9 7.8 93 11 30 31 >10,000 9 6.9 6.6 177 110 27 158 344 LSZ 0.4 2.4 ? 276 19 27 37 >10,000 27 15 14 292 74 6 96 402 Lisuride 0.3 16 >10,000 44 5.4 2.9 >10,000 >10,000 3.1 7.3 6.8 >10,000 6.7 136 3.8 77

History

Lysergamides, such as ergine, isoergine, and ergometrine, were discovered by the early 1930s, and LSD was discovered by 1938 and its hallucinogenic effects in 1943 by Albert Hofmann. Many synthetic lysergamide analogues of LSD, modified at the amide and/or 1 or 2 positions, were first described by Hofmann and colleagues in the mid-to-late 1950s. N(6)-Substituted lysergamides were first reported in 1970 and thereafter in the 1970s and 1980s by multiple groups, including Hofmann and colleagues, Yuji Nakahara and Tetsukichi Niwaguchi and colleagues, and David E. Nichols and colleagues. The psychedelic effects of N(6)-substituted lysergamides were reported by Alexander Shulgin in 1986 and thereafter. Additional novel lysergamides modified at the amide, like LA-3Cl-SB and LA-Aziridine, were described by Nichols and Robert Oberlender and colleagues in the late 1980s, while LSZ (LA-Azetidine) was described by the same group in 2002. Numerous 1-substituted LSD prodrugs such as 1P-LSD and 1V-LSD and other psychedelic lysergamides were developed by Lizard Labs in the 2010s and 2020s.

List of lysergamides