Lysergamides

Lysergamides, also known as ergoamides^[1][2] 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.^[3]

The lysergamide core, with common substitution positions denoted.

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.^{[4][5][6][7][8][9][10][11][12][13][14][15][16]} 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.

The lysergamides, such as ergine, isoergine, and ergometrine, were discovered by the early 1930s,^[17][18][19] and LSD was discovered by 1938 and its hallucinogenic effects in 1943 by Albert Hofmann.^[20][21]

Simplified or partial ergolines and lysergamides, such as NDTDI, DEMPDHPCA, and N-DEAOP-NMT, are also known.^[22][23][24]

Use and effects

The dosages, potencies, durations, and effects of lysergamides have been reviewed by Alexander Shulgin.^{[25][26][27][28][29]} They have also been reviewed by Albert Hofmann,^[30] David E. Nichols,^[31] and other researchers.^{[32][33][34][35][36][37][38][39][40]}

Doses, potencies, and durations of LSD and its analogues

Common name	Code	Dose (mg)	Potency (×LSD)	Duration (h)
Lysergic acid amide (LSA; ergine)	LA-111	0.5–6	≤0.1	~4–10
Isolysergic acid amide (iso-LSA; isoergine)	Iso-LA-819	2–5	<0.1	~4–10
Lysergic acid methylamide	LAM	~0.5	≤0.2	?
Lysergic acid dimethylamide	DAM-57	0.5–1.2	0.1	?
Lysergic acid ethylamide	LAE-32	0.5–1.6	≤0.1	?
1-Acetyllysergic acid ethylamide	ALA-10	~1.2	≤0.1	?
1-Methyllysergic acid ethylamide	MLA-74	~2	0.05	?
Lysergic acid isopropylamide	LAiP	?	?	?
Lysergic acid methylethylamide	LME-54	?	~0.33	?
Lysergic acid diethylamide (LSD)	LSD-25, METH-LAD	0.05–0.2	1	8–12
Isolysergic acid diethylamide	Iso-LSD	>4	<0.02	?
2,3-Dihydro-LSD	2,3-DH-LSD	~0.15–0.4	~0.15	~8–12
9,10-Dihydro-LSD	9,10-DH-LSD	>2.5	<0.02	?
2-Bromo-LSD	BOL-148	>1 (≥6–20)	<0.1 (≤0.005–0.02)	?
2-Iodo-LSD	IOL	?	?	?
2-Keto-LSD (2-oxy-LSD)	?	>0.3	?	?
1-Acetyl-LSD	ALD-52	0.1–0.2	1	?
1-Methyl-LSD	MLD-41	0.2–0.3	0.3	?
1-Hydroxymethyl-LSD	OML-632	?	~0.7	?
1-Methyl-2-bromo-LSD	MBL-61	>10	<0.01	?
1-Methyl-2-iodo-LSD	MIL	?	?	?
Lysergic acid propylamide	LAP	>0.5	<0.2	?
Lysergic acid methylpropylamide	LMP	>0.1	<1	?
Lysergic acid ethylpropylamide	LEP-57	?	~0.33	?
Lysergic acid dipropylamide	DPL	>1	<0.1	?
Lysergic acid dibutylamide	LBB-66	?	0	?
Lysergic acid diallylamide	DAL	>1	<0.1	?
Ergonovine (ergometrine)a	–	5–10	≤0.01	?
Methylergonovine (methylergometrine)b	–	2	0.05	?
Methysergidec	UML-491	4–8	0.02	?
Lysergic acid piperidide	LA-Pip	?	?	?
Lysergic acid pyrrolidide	LPD-824	~0.8	0.05–0.1	?
Lysergic acid pyrrolinide	LPN	?	?	?
1-Methyllysergic acid pyrrolidide	MPD-75	>1.6	≤0.1	?
Lysergic acid morpholide	LSM-775, SLM	0.3–0.6	0.1–0.3	?
Lysergic acid 2,4-dimethylazetidide	LA-SS-Az, LSZ	0.1–0.3	0.5	?
Nor-LSD (6-nor-LSD)	H-LAD	>0.5	<0.2	?
6-Ethyl-nor-LSD	ETH-LAD	0.04–0.15	2	8–12
6-Propyl-nor-LSD	PRO-LAD	0.08–0.2	1	6–8
6-Allyl-nor-LSD	AL-LAD, ALLY-LAD	0.05–0.16	1	6–8
6-n-Butyl-nor-LSD	BU-LAD	≥0.4–0.5	<0.3	?
6-Propynyl-nor-LSD	PARGY-LAD	0.16–0.5	0.2–0.6	?
6-(β-Phenethyl)-nor-LSD	PHENETHY-LAD	>0.35–0.5	<0.3	?
Footnotes: a = Ergonovine is lysergic acid hydroxyisopropylamide. b = Methylergonovine is lysergic acid hydroxy-sec-butylamide. c = Methysergide is 1-methylmethylergonovine (1-methyllysergic acid hydroxy-sec-butylamide). Refs: Main: [25][26][27][28][29][41][42][43][39][40][17][33][34][37][36][44] Additional: [45][46][47]

History

Many synthetic lysergamide analogues of LSD were first described by Albert Hofmann and colleagues by 1955.^[48]

List of lysergamides

Lysergamides, tabulated by structure

Structure	Name (synonyms)	CAS #	R1	R6	R2	R3	Other
	Ergine (lysergic acid amide, lysergamide)	478-94-4	H	CH3	H	H	-
	Isoergine (isolysergic acid amide, isolysergamide)	2889-26-1	H	CH3	H	H	8-epi
	DAM-57 (lysergic acid dimethylamide)	4238-84-0	H	CH3	CH3	CH3	-
	Ergometrine (ergonovine; lysergic acid propanolamide)	60-79-7	H	CH3	CH(CH3)CH2OH	H	-
	Propisergide (1-methylergonovine)	5793-04-4	CH3	CH3	CH(CH3)CH2OH	H	-
	Ergotamine (an ergopeptine)	113-15-5	H	CH3	--	C17H18N2O4	-
	Methylergometrine (methylergonovine; lysergic acid butanolamide)	113-42-8	H	CH3	CH(CH2CH3)CH2OH	H	-
	Methysergide (1-methyl-lysergic acid butanolamide)	361-37-5	CH3	CH3	CH(CH2CH3)CH2OH	H	-
	Amesergide (9,10-dihydro-11-isopropyllysergic acid cyclohexylamide)	121588-75-8	CH(CH3)2	CH3	C6H11	H	-
	LY-215840 (1-isopropyl-9,10-dihydro-N-(2-hydroxycyclopent-anyl)lysergamide)	137328-52-0	CH(CH3)2	CH3	C5H8OH	H	-
	Cabergoline (N-[3-(dimethylamino)propyl]-N-(ethylcarbamoyl)-6-(prop-2-en-1-yl)-9,10-dihydrolysergamide)	81409-90-7	H	H2C=CH-CH2	CONHCH2CH3	CH2CH2CH2N(CH3)2	-
	LAE-32 (lysergic acid ethylamide)	478-99-9	H	CH3	CH2CH3	H	-
	LAiP (lysergic acid isopropylamide)		H	CH3	CH(CH3)2	H	-
	LAtB (lysergic acid tert-butylamide)		H	CH3	C(CH3)3	H	-
	LAcB (lysergic acid cyclobutylamide)		H	CH3	(CH2)4	H	-
	Cepentil (lysergic acid cyclopentylamide)		H	CH3	(CH2)5	H	-
	LSB (lysergic acid 2-butylamide)	137765-82-3	H	CH3	CH(CH3)CH2CH3	H	-
	LSP (lysergic acid 3-pentylamide)		H	CH3	CH(CH2CH3)CH2CH3	H	-
	DPL (lysergic acid dipropylamide)		H	CH3	CH2CH2CH3	CH2CH2CH3	-
	DAL (lysergic acid diallylamide)		H	CH3	H2C=CH-CH2	H2C=CH-CH2	-
	MIPLA (lysergic acid methylisopropylamide)	100768-08-9	H	CH3	CH(CH3)2	CH3	-
	EIPLA (lysergic acid ethylisopropylamide)		H	CH3	CH(CH3)2	CH2CH3	-
	ECPLA (lysergic acid ethylcyclopropylamide)		H	CH3	C3H5	CH2CH3	-
	LEO (lysergic acid ethyl-2-hydroxyethylamide)	65527-58-4	H	CH3	CH2CH2OH	CH2CH3	-
	LA-MeO[49]		H	CH3	CH2CH2OCH3	CH2CH3	-
	ETFELA (lysergic acid N-ethyl-N-(2,2,2-trifluoroethyl)amide)		H	CH3	CH2CF3	CH2CH3	-
	WO 2022/008627 Compound 4; TRALA-04[50]		H	CH3	CH2CH2F	CH2CH3	-
	WO 2022/226408 Example 29[51]; TRALA-08		H	CH3	CH2CH2F	CH2CH2F	-
	LA-3Cl-SB (lysergic acid N-(3-chloro-sec-butyl)amide)		H	CH3	CH(CH3)CClHCH3	H	-
	LAMPA (lysergic acid methylpropylamide)	40158-98-3	H	CH3	CH2CH2CH3	CH3	-
	EPLA (lysergic acid ethylpropylamide; LEP-57)		H	CH2CH3	CH2CH2CH3	CH3	-
	LSD (lysergic acid diethylamide; LAD)	50-37-3	H	CH3	CH2CH3	CH2CH3	-
	Iso-LSD	2126-78-5	H	CH3	CH2CH3	CH2CH3	8-epi
	Nor-LSD (6-nor-LSD)	35779-43-2	H	H	CH2CH3	CH2CH3	-
	ETH-LAD (6-ethyl-6-nor-LSD)	65527-62-0	H	CH2CH3	CH2CH3	CH2CH3	-
	PARGY-LAD (6-propynyl-6-nor-LSD)		H	HC≡C−CH2	CH2CH3	CH2CH3	-
	AL-LAD (6-allyl-6-nor-LSD)	65527-61-9	H	H2C=CH-CH2	CH2CH3	CH2CH3	-
	PRO-LAD (6-propyl-6-nor-LSD)	65527-63-1	H	CH2CH2CH3	CH2CH3	CH2CH3	-
	IP-LAD (6-isopropyl-6-nor-LSD)		H	CH(CH3)2	CH2CH3	CH2CH3	-
	CYP-LAD (TRALA-22; 6-cyclopropyl-6-nor-LSD)		H	C3H5	CH2CH3	CH2CH3	-
	CPM-LAD (WO 2022/226408 Example 13)		H	CH2C3H5	CH2CH3	CH2CH3	-
	BU-LAD (6-butyl-6-nor-LSD)	96930-87-9	H	CH2CH2CH2CH3	CH2CH3	CH2CH3	-
	PHENETHY-LAD (6-phenethyl-6-nor-LSD)		H	CH2CH2C6H5	CH2CH3	CH2CH3	-
	NBOMe-LAD (WO 2022/226408 Example 10)		H	CH2C6H4-o-OCH3	CH2CH3	CH2CH3	-
	FLUORETH-LAD (FE-LAD; TRALA-15; 6-(2-fluoroethyl)-6-nor-LSD)		H	CH2CH2F	CH2CH3	CH2CH3	-
	FP-LAD (WO 2022/226408 Example 2; TRALA-16; 6-(3-fluoropropyl)-6-nor-LSD)		H	CH2CH2CH2F	CH2CH3	CH2CH3	-
	CE-LAD (CHLORETH-LAD; 6-(2-chloroethyl)-6-nor-LSD)		H	CH2CH2Cl	CH2CH3	CH2CH3	-
	ALD-52 (1-acetyl-LSD)	3270-02-8	COCH3	CH3	CH2CH3	CH2CH3	-
	1P-LSD (1-propionyl-LSD)	2349358-81-0	COCH2CH3	CH3	CH2CH3	CH2CH3	-
	1B-LSD (1-butanoyl-LSD)	2349376-12-9	COCH2CH2CH3	CH3	CH2CH3	CH2CH3	-
	1V-LSD (1-valeryl-LSD)		CO(CH2)3CH3	CH3	CH2CH3	CH2CH3	-
	1H-LSD (1-hexanoyl-LSD)		CO(CH2)4CH3	CH3	CH2CH3	CH2CH3	-
	1DD-LSD (1-dodecanoyl-LSD)		CO(CH2)10CH3	CH3	CH2CH3	CH2CH3	-
	1cP-LSD (1-cyclopropylmethanoyl-LSD)		COC3H5	CH3	CH2CH3	CH2CH3	-
	1D-LSD (1-(1,2-dimethylcyclobutane-1-carbonyl)-LSD)		COC4H5(CH3)2	CH3	CH2CH3	CH2CH3	-
	1F-LSD (1-(furan-2-carbonyl)-LSD) [52]		COC4H3O	CH3	CH2CH3	CH2CH3	-
	1T-LSD (1-(thiophene-2-carbonyl)-LSD)		COC4H3S	CH3	CH2CH3	CH2CH3	-
	1S-LSD (1-(3-(trimethylsilyl)propionyl)-LSD)		CO(CH2)2Si(CH3)3	CH3	CH2CH3	CH2CH3	-
	1P-AL-LAD (1-propionyl-6-allyl-6-nor-LSD)		COCH2CH3	H2C=CH-CH2	CH2CH3	CH2CH3	-
	1cP-AL-LAD (1-cyclopropylmethanoyl-6-allyl-6-nor-LSD)		COC3H5	H2C=CH-CH2	CH2CH3	CH2CH3	-
	1T-AL-LAD (1-(2-thienoyl)-6-allyl-6-nor-LSD)[53]		COC4H3S	H2C=CH-CH2	CH2CH3	CH2CH3	-
	1P-ETH-LAD (1-propionyl-6-ethyl-6-nor-LSD)		COCH2CH3	CH2CH3	CH2CH3	CH2CH3	-
	1P-MIPLA (1-propionyl-lysergic acid methylisopropylamide)		COCH2CH3	CH3	CH(CH3)2	CH3	-
	MLD-41 (1-methyl-LSD)	4238-85-1	CH3	CH3	CH2CH3	CH2CH3	-
	OML-632 (1-hydroxymethyl-LSD)	114004-70-5	CH2OH	CH3	CH2CH3	CH2CH3	-
	LSM-775 (lysergic acid morpholide)	4314-63-0	H	CH3	CH2CH2-O-CH2CH2		-
	LPD-824 (lysergic acid pyrrolidide)	2385-87-7	H	CH3	(CH2)4		-
	MPD-75 (1-methyllysergic acid pyrrolidide)	7221-79-6	CH3	CH3	(CH2)4		-
	Lysergic acid pyrrolinide	?	H	CH3	CH2-CH=CH-CH2		-
	LA-Cispyr	?	H	CH3	cis-CH(CH3)-CH2CH2-CH(CH3)		-
	LA-Pip (lysergic acid piperidide)	50485-23-9	H	CH3	(CH2)5		-
	LSD-Azepane (lysergic acid azepane)[54]		H	CH3	(CH2)6		-
	Lysergic acid 2,4-dimethylazetidide (LA-SS-Az, LSZ)	470666-31-0	H	CH3	CH2(CHCH3)2CH2		-
	WO 2022/008627 Compound 1 [55]		H	CH3	(CH2)2C(CH2)2O		-
	Lysergic acid-(2,3-dimethylaziridinyl)amide (LA-Aziridine)	?	H	CH3	?		-
	2-Bromo-LSD (BOL-148; bromolysergide)	478-84-2	H	CH3	CH2CH3	CH2CH3	2-Br
	1P-BOL-148 (1-propionyl-2-bromo-LSD)		COCH2CH3	CH3	CH2CH3	CH2CH3	2-Br
	12-Hydroxy-LSD (12-OH-LSD)	60573-89-9	H	CH3	CH2CH3	CH2CH3	12-OH
	12-Methoxy-LSD (12-MeO-LSD)	50484-99-6	H	CH3	CH2CH3	CH2CH3	12-OMe
	13-Fluoro-LSD[56]		H	CH3	CH2CH3	CH2CH3	13-F
	13-Hydroxy-LSD		H	CH3	CH2CH3	CH2CH3	13-OH
	14-Hydroxy-LSD[57]		H	CH3	CH2CH3	CH2CH3	14-OH

Related compounds

See also: List of miscellaneous 5-HT2A receptor agonists

Structure	Name	Chemical name	CAS #
	2,3-Dihydro-LSD (2,3-DH-LSD)	(6aR,9R)-N,N-diethyl-7-methyl-5,5a,6,6a,8,9-hexahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
	9,10-Dihydro-LSD (9,10-DH-LSD)	(6aR,9R)-N,N-diethyl-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide	3031-47-8
	Bromerguride	1,1-diethyl-3-(2-bromo-9,10-didehydro-6-methyl-8α-ergolinyl)urea	83455-48-5
	Descarboxylysergic acid	6-methyl-9,10-didehydroergoline	51867-17-5
	Disulergine	(6aR,9S,10aR)-9-(dimethylsulfamoylamino)-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline	59032-40-5
	Dosergoside[58]	(6aR,9R,10aR)-N-[(E,2S,3R)-1,3-dihydroxyoctadec-4-en-2-yl]-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide	87178-42-5
	Ergoline	(6aR)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline	478-88-6
	Etisulergine[59]	(6aR,9S,10aR)-9-(diethylsulfamoylamino)-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline	64795-23-9
	GYKI-32887	N-[[(6aR,10aR)-7-methyl-6,6a,8,10a-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]methyl]-N-(2-azidoethyl)methanesulfonamide	78463-86-2
	JRT	(7S)-N,N-diethyl-6-methyl-6,9-diazatetracyclo[7.6.1.02,7.012,16]hexadeca-1(15),2,10,12(16),13-pentaene-4-carboxamide	?
	Lysergine	9,10-didehydro-6,8β-dimethylergoline	519-10-8
	Lysergol	(6-methyl-9,10-didehydroergolin-8β-yl)methanol	1413-67-8
	Lysergic acid	6-methyl-9,10-didehydroergoline-8β-carboxylic acid	82-58-6
	Lergotrile	2-[(6aR,9S,10aR)-5-chloro-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinolin-9-yl]acetonitrile	36945-03-6
	Lisuride	1,1-diethyl-3-(6-methyl-9,10-didehydroergolin-8α-yl)urea	18016-80-3
	Proteguride[60][61]	1,1-diethyl-3-(6-n-propyl-8α-ergolinyl)urea	?
	Terguride	N,N-diethyl-N'-[(8α)-6-methylergolin-8-yl]urea	37686-84-3

See also

• Ergoline
• Partial lysergamide
• Substituted tryptamine
• Substituted phenethylamine