Lysergamides

Class of chemical compounds

Amides of lysergic acid are collectively known as lysergamides, and include a number of compounds with potent agonist and/or antagonist activity at various serotonin and dopamine receptors. Lysergamides contain an embedded tryptamine structure, and as a result can produce similar, often psychedelic, effects to those of the true tryptamines. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]

General structure of Lysergamides
Lysergamides, tabulated by structure
Structure Name CAS number R1 R6 R2 R3 Other
LSA / LAA 478-94-4 H CH3 H H -
DAM-57 4238-84-0 H CH3 CH3 CH3 -
Ergometrine (Ergonovine) 60-79-7 H CH3 CH(CH3)CH2OH H -
Ergotamine 113-15-5 H CH3 -- C17H18N2O4 -
Methergine 113-42-8 H CH3 CH(CH2CH3)CH2OH H -
Methysergide 361-37-5 CH3 CH3 CH(CH2CH3)CH2OH H -
Amesergide 121588-75-8 CH(CH3)2 CH3 C6H11 H -
LY-215840 137328-52-0 CH(CH3)2 CH3 C5H8OH H -
Cabergoline 81409-90-7 H H2C=CH-CH2 CONHCH2CH3 CH2CH2CH2N(CH3)2 -
LAE-32 478-99-9 H CH3 CH2CH3 H -
LAiP H CH3 CH(CH3)2 H -
LAtB H CH3 C(CH3)3 H -
LAcB H CH3 (CH2)4 H -
Cepentil H CH3 (CH2)5 H -
LSB 137765-82-3 H CH3 CH(CH3)CH2CH3 H -
LSP H CH3 CH(CH2CH3)CH2CH3 H -
DAL H CH3 H2C=CH-CH2 H2C=CH-CH2 -
MIPLA 100768-08-9 H CH3 CH(CH3)2 CH3 -
EIPLA H CH3 CH(CH3)2 CH2CH3 -
ECPLA H CH3 C3H5 CH2CH3 -
ETFELA H CH3 CH2CF3 CH2CH3 -
LAMPA 40158-98-3 H CH3 CH2CH2CH3 CH3 -
EPLA H CH2CH3 CH2CH2CH3 CH3 -
LSD / LAD 50-37-3 H CH3 CH2CH3 CH2CH3 -
ETH-LAD 65527-62-0 H CH2CH3 CH2CH3 CH2CH3 -
PARGY-LAD H HC≡C−CH2 CH2CH3 CH2CH3 -
AL-LAD 65527-61-9 H H2C=CH-CH2 CH2CH3 CH2CH3 -
PRO-LAD 65527-63-1 H CH2CH2CH3 CH2CH3 CH2CH3 -
IP-LAD H CH(CH3)2 CH2CH3 CH2CH3 -
CYP-LAD[16] H C3H5 CH2CH3 CH2CH3 -
BU-LAD 96930-87-9 H CH2CH2CH2CH3 CH2CH3 CH2CH3 -
FLUORETH-LAD[17] H CH2CH2F CH2CH3 CH2CH3 -
ALD-52 3270-02-8 COCH3 CH3 CH2CH3 CH2CH3 -
1P-LSD 2349358-81-0 COCH2CH3 CH3 CH2CH3 CH2CH3 -
1B-LSD 2349376-12-9 COCH2CH2CH3 CH3 CH2CH3 CH2CH3 -
1V-LSD CO(CH2)3CH3 CH3 CH2CH3 CH2CH3 -
1cP-LSD[18] COC3H5 CH3 CH2CH3 CH2CH3 -
1D-LSD COC4H5(CH3)2 CH3 CH2CH3 CH2CH3 -
1P-AL-LAD COCH2CH3 H2C=CH-CH2 CH2CH3 CH2CH3 -
1cP-AL-LAD COC3H5 H2C=CH-CH2 CH2CH3 CH2CH3 -
1P-ETH-LAD COCH2CH3 CH2CH3 CH2CH3 CH2CH3 -
1P-MIPLA COCH2CH3 CH3 CH(CH3)2 CH3 -
MLD-41 4238-85-1 CH3 CH3 CH2CH3 CH2CH3 -
LSM-775 4314-63-0 H CH3 CH2CH2-O-CH2CH2 -
LPD-824 2385-87-7 H CH3 (CH2)4 -
LSD-Pip 50485-23-9 H CH3 (CH2)5 -
LSD-Azapane H CH3 (CH2)6 -
LA-SS-Az 470666-31-0 H CH3 CH2(CHCH3)2CH2 -
2-Bromo-LSD 478-84-2 H CH3 CH2CH3 CH2CH3 2-Br
12-Methoxy-LSD[19] 50484-99-6 H CH3 CH2CH3 CH2CH3 12-OMe
13-Fluoro-LSD[20] H CH3 CH2CH3 CH2CH3 13-F
14-Hydroxy-LSD[21] H CH3 CH2CH3 CH2CH3 14-OH

See also

References

  1. ^ Hofmann A (June 1959). "Psychotomimetic drugs; chemical and pharmacological aspects". Acta Physiologica et Pharmacologica Neerlandica. 8: 240–58. PMID 13852489.
  2. ^ US patent 2997470, Pioch RP, "LYSERGIC ACID AMIDES", published 1956-03-05, issued 1961-08-22 
  3. ^ Hoffman AJ, Nichols DE (September 1985). "Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives". Journal of Medicinal Chemistry. 28 (9): 1252–1255. doi:10.1021/jm00147a022. PMID 4032428.
  4. ^ Huang X, Marona-Lewicka D, Pfaff RC, Nichols DE (March 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. S2CID 16490010.
  5. ^ Watts VJ, Lawler CP, Fox DR, Neve KA, Nichols DE, Mailman RB (April 1995). "LSD and structural analogs: pharmacological evaluation at D1 dopamine receptors". Psychopharmacology. 118 (4): 401–409. doi:10.1007/BF02245940. PMID 7568626. S2CID 21484356.
  6. ^ Nichols DE, Frescas S, Marona-Lewicka D, Kurrasch-Orbaugh DM (September 2002). "Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of the diethylamide moiety in the potent hallucinogenic agent N,N-diethyllysergamide (LSD)". Journal of Medicinal Chemistry. 45 (19): 4344–4349. doi:10.1021/jm020153s. PMID 12213075.
  7. ^ Schiff PL (October 2006). "Ergot and its alkaloids". American Journal of Pharmaceutical Education. 70 (5): 98. doi:10.5688/aj700598. PMC 1637017. PMID 17149427.
  8. ^ Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A (2008). "The pharmacology of lysergic acid diethylamide: a review". CNS Neuroscience & Therapeutics. 14 (4): 295–314. doi:10.1111/j.1755-5949.2008.00059.x. PMC 6494066. PMID 19040555.
  9. ^ Nichols DE (2017). "Chemistry and Structure-Activity Relationships of Psychedelics". Current Topics in Behavioral Neurosciences. 36: 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524.
  10. ^ Brandt SD, Kavanagh PV, Westphal F, Stratford A, Elliott SP, Hoang K, et al. (September 2016). "Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD)". Drug Testing and Analysis. 8 (9): 891–902. doi:10.1002/dta.1884. PMC 4829483. PMID 26456305.
  11. ^ Brandt SD, Kavanagh PV, Westphal F, Elliott SP, Wallach J, Colestock T, et al. (January 2017). "Return of the lysergamides. Part II: Analytical and behavioural characterization of N6 -allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ)". Drug Testing and Analysis. 9 (1): 38–50. doi:10.1002/dta.1985. PMC 5411264. PMID 27265891.
  12. ^ Brandt SD, Kavanagh PV, Westphal F, Elliott SP, Wallach J, Stratford A, et al. (October 2017). "Return of the lysergamides. Part III: Analytical characterization of N6 -ethyl-6-norlysergic acid diethylamide (ETH-LAD) and 1-propionyl ETH-LAD (1P-ETH-LAD)". Drug Testing and Analysis. 9 (10): 1641–1649. doi:10.1002/dta.2196. PMC 6230477. PMID 28342178.
  13. ^ Brandt SD, Kavanagh PV, Twamley B, Westphal F, Elliott SP, Wallach J, et al. (February 2018). "Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775)". Drug Testing and Analysis. 10 (2): 310–322. doi:10.1002/dta.2222. PMC 6230476. PMID 28585392.
  14. ^ Brandt SD, Kavanagh PV, Westphal F, Stratford A, Elliott SP, Dowling G, et al. (August 2019). "Return of the lysergamides. Part V: Analytical and behavioural characterization of 1-butanoyl-d-lysergic acid diethylamide (1B-LSD)". Drug Testing and Analysis. 11 (8): 1122–1133. doi:10.1002/dta.2613. PMC 6899222. PMID 31083768.
  15. ^ Halberstadt AL, Klein LM, Chatha M, Valenzuela LB, Stratford A, Wallach J, et al. (February 2019). "Pharmacological characterization of the LSD analog N-ethyl-N-cyclopropyl lysergamide (ECPLA)". Psychopharmacology. 236 (2): 799–808. doi:10.1007/s00213-018-5055-9. PMC 6848745. PMID 30298278.
  16. ^ Kruegel AC. Novel Ergolines and Methods of Treating Mood Disorders. Patent WO 2022/226408
  17. ^ WO 2022/008627, Grill M, "Improved Method for the Production of Lysergic Acid Diethylamide (LSD) and Novel Derivatives thereof." 
  18. ^ Brandt SD, Kavanagh PV, Westphal F, Stratford A, Odland AU, Klein AK, et al. (June 2020). "Return of the lysergamides. Part VI: Analytical and behavioural characterization of 1-cyclopropanoyl-d-lysergic acid diethylamide (1CP-LSD)". Drug Testing and Analysis. 12 (6): 812–826. doi:10.1002/dta.2789. PMC 9191646. PMID 32180350.
  19. ^ Usdin E, Efron DH. Psychotropic Drugs and Related Compounds. (1972) ASIN B002X3CDIY
  20. ^ WO 2021/076572, Olson DE, et al., "Ergoline-like compounds for promoting neural plasticity" 
  21. ^ Libânio Osório Marta RF (August 2019). "Metabolism of lysergic acid diethylamide (LSD): an update". Drug Metabolism Reviews. 51 (3): 378–387. doi:10.1080/03602532.2019.1638931. PMID 31266388.
  • v
  • t
  • e
Psychedelics
(5-HT2A
agonists)
Benzofurans
Lyserg‐
amides
Phenethyl‐
amines
2C-x
25x-NBx
25x-NB
25x-NB3OMe
  • 25B-NB3OMe
  • 25C-NB3OMe
  • 25D-NB3OMe
  • 25E-NB3OMe
  • 25H-NB3OMe
  • 25I-NB3OMe
  • 25N-NB3OMe
  • 25P-NB3OMe
  • 25T2-NB3OMe
  • 25T4-NB3OMe
  • 25T7-NB3OMe
  • 25TFM-NB3OMe
25x-NB4OMe
  • 25B-NB4OMe
  • 25C-NB4OMe
  • 25D-NB4OMe
  • 25E-NB4OMe
  • 25H-NB4OMe
  • 25I-NB4OMe
  • 25N-NB4OMe
  • 25P-NB4OMe
  • 25T2-NB4OMe
  • 25T4-NB4OMe
  • 25T7-NB4OMe
  • 25TFM-NB4OMe
25x-NBF
25x-NBMD
  • 25B-NBMD
  • 25C-NBMD
  • 25D-NBMD
  • 25E-NBMD
  • 25F-NBMD
  • 25H-NBMD
  • 25I-NBMD
  • 25P-NBMD
  • 25T2-NBMD
  • 25T7-NBMD
  • 25TFM-NBMD
25x-NBOH
25x-NBOMe
Atypical structures
25x-NMx
  • 25B-NMe7BF
  • 25B-NMe7BT
  • 25B-NMe7Bim
  • 25B-NMe7Box
  • 25B-NMe7DHBF
  • 25B-NMe7Ind
  • 25B-NMe7Indz
  • 25B-NMePyr
  • 25I-NMe7DHBF
  • 25I-NMeFur
  • 25I-NMeTHF
  • 25I-NMeTh
N-(2C)-fentanyl
  • N-(2C-B) fentanyl
  • N-(2C-C) fentanyl
  • N-(2C-D) fentanyl
  • N-(2C-E) fentanyl
  • N-(2C-G) fentanyl
  • N-(2C-H) fentanyl
  • N-(2C-I) fentanyl
  • N-(2C-IP) fentanyl
  • N-(2C-N) fentanyl
  • N-(2C-P) fentanyl
  • N-(2C-T) fentanyl
  • N-(2C-T-2) fentanyl
  • N-(2C-T-4) fentanyl
  • N-(2C-T-7) fentanyl
  • N-(2C-TFM) fentanyl
3C-x
4C-x
DOx
HOT-x
MDxx
Mescaline (subst.)
TMAs
  • TMA
  • TMA-2
  • TMA-3
  • TMA-4
  • TMA-5
  • TMA-6
Others
Piperazines
Tryptamines
alpha-alkyltryptamines
x-DALT
x-DET
x-DiPT
x-DMT
x-DPT
Ibogaine-related
x-MET
x-MiPT
Others
Others
Dissociatives
(NMDAR
antagonists)
Arylcyclo‐
hexylamines
Ketamine-related
PCP-related
Others
Adamantanes
Diarylethylamines
Morphinans
Others
Deliriants
(mAChR
antagonists)
Others
Cannabinoids
(CB1 agonists)
Natural
Synthetic
AM-x
CP x
HU-x
JWH-x
Misc. designer cannabinoids
D2 agonists
GABAA
enhancers
Inhalants
(Mixed MOA)
κOR agonists
Oneirogens
Others
  • v
  • t
  • e
α1
Agonists
Antagonists
α2
Agonists
Antagonists
β
Agonists
Antagonists
  • See also: Receptor/signaling modulators
  • Dopaminergics
  • Serotonergics
  • Monoamine reuptake inhibitors
  • Monoamine releasing agents
  • Monoamine metabolism modulators
  • Monoamine neurotoxins
  • v
  • t
  • e
D1-like
Agonists
PAMs
Antagonists
D2-like
Agonists
Antagonists
  • See also: Receptor/signaling modulators
  • Adrenergics
  • Serotonergics
  • Monoamine reuptake inhibitors
  • Monoamine releasing agents
  • Monoamine metabolism modulators
  • Monoamine neurotoxins
  • v
  • t
  • e
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT37
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
  • See also: Receptor/signaling modulators
  • Adrenergics
  • Dopaminergics
  • Melatonergics
  • Monoamine reuptake inhibitors and releasing agents
  • Monoamine metabolism modulators
  • Monoamine neurotoxins
  • v
  • t
  • e
TAAR1
Agonists
Endogenous
Synthetic
Neutral antagonists
  •  
Inverse agonists
TAAR2
Agonists
 
Neutral antagonists
  •  
TAAR5
Agonists
Neutral antagonists
  •  
Inverse agonists
References for all endogenous human TAAR1 ligands are provided at List of trace amines


References for synthetic TAAR1 agonists can be found at TAAR1 or in the associated compound articles. For TAAR2 and TAAR5 agonists and inverse agonists, see TAAR for references.


See also: Receptor/signaling modulators
  • v
  • t
  • e
Lysergic acid
derivatives
Psychedelic
lysergamides
Clavines
Other
ergolines
Natural
sources

Morning glory: Argyreia nervosa (Hawaiian Baby Woodrose), Ipomoea spp.(Morning Glory, Tlitliltzin, Badoh Negro), Rivea corymbosa (Coaxihuitl, Ololiúqui)