Isoergine

Isoergine
Clinical data
Other names	Isolysergic acid amide; D-Isolysergic acid amide; Erginine; Isolysergamide; (+)-Isolysergic acid amide; Iso-LA; Iso-LA-819; Iso-LSA; d-Isolysergamide; 6-Methyl-9,10-didehydroergoline-8α-carboxamide
Routes of; administration	Oral
Drug class	Serotonin receptor modulator; Serotonergic psychedelic; Hallucinogen
ATC code	None;
Identifiers
	IUPAC name (6aR,9S)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide;
CAS Number	2889-26-1;
PubChem CID	12309749;
ChemSpider	32698654;
UNII	90DGH6Y8E9;
CompTox Dashboard (EPA)	DTXSID80183082 ;
Chemical and physical data
Formula	C16H17N3O
Molar mass	267.332 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN1C[C@H](C=C2[C@H]1CC3=CNC4=CC=CC2=C34)C(=O)N;
	InChI InChI=1S/C16H17N3O/c1-19-8-10(16(17)20)5-12-11-3-2-4-13-15(11)9(7-18-13)6-14(12)19/h2-5,7,10,14,18H,6,8H2,1H3,(H2,17,20)/t10-,14+/m0/s1; Key:GENAHGKEFJLNJB-IINYFYTJSA-N;

Isoergine, also known as isolysergic acid amide (iso-LSA or iso-LA-819), isolysergamide, or erginine, is a serotonergic psychedelic of the ergoline and lysergamide families related to ergine (lysergic acid amide; LSA) and lysergic acid diethylamide (LSD).^[2]^[3]^[4]^[5]^[1] It is the epimer of ergine inverted at the 8 position.^[5]^[6]^[7]^[8] Along with ergine and other ergolines, isoergine occurs naturally in morning glories.^[2]^[3]^[4]^[5]^[1]^[8] It is thought to be primarily responsible for the hallucinogenic effects of morning glory seeds.^[3]^[1]^[2]^[4]^[6]^[9]

^ ^a ^b ^c ^d Brimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. OL 4850660M. d-Lysergic acid amide (ergine) is the major constituent of the seeds of both Rivea corymbosa and Ipomoea violacea, together with smaller amounts of d-isolysergic acid amide (isoergine), chanoclavine, elymoclavine, and the N-(1-hydroxyethyl)amides of lysergic and isolysergic acids. [...] Lysergol is found in Rivea but not in Ipomoea, while ergometrine (ergonovine) is present in the latter but not the former (Hofmann and Tscherter, 1960; Hofmann, 1961b, 1964; Hofmann and Cerletti, 1961; Greger, 1963). [...] The constituents of these convolvulaceous plants were not new even in 1960; the isomeric lysergic acid amides had previously been obtained as cleavage products by hydrolysis of the ergot alkaloids (Smith and Timmis, 1932, 1936), [...] the isomeric amides had also been synthesized in the laboratories of the Sandoz group (Stoll, Hofmann, and Schlientz, 1949). It is clear that the pharmacologically active constituents of ololiuqui are the isomeric lysergic acid amides. [...] Oral doses of 2 mg. of isolysergic acid amide are reported to produce a feeling of mental emptiness and total detachment from the outside world. Heim and his colleagues suggest that the overall effects of ololiuqui are due to these two compounds, the d-lysergic acid amide giving intoxication with strong autonomic side-effects and the d-isolysergic acid amide producing some euphoria, synaesthesia, and altered time experience. Certainly elymoclavine, lysergol, chanoclavine, and ergometrine produce no psychic changes in man (Isbell and Gorodetzky, 1966; Hofmann, 1968), though the first two do produce central excitation in animals (Yui and Takeo, 1958). Moreover, the time-course of absorption and distribution of d-isolysergic acid amide in rat brain exactly paralleled the course of behavioural aberrations produced by intraperitoneal doses of 5 mg./kg. (Vogel, Carapellotti, Evans, and Der Marderosian, 1972). [...] Five-hundred seeds of certain ornamental Ipomoea varieties contain as much as 1 mg. of ergometrine, which is usually considered to be an effective oxytocic in doses as low as 0·2-0·5 mg.
^ ^a ^b ^c Fanchamps A (1978). "Some Compounds With Hallucinogenic Activity". In Berde B, Schild HO (eds.). Ergot Alkaloids and Related Compounds. Handbook of Experimental Pharmacology (HEP). Vol. 49. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 567–614. doi:10.1007/978-3-642-66775-6_8. ISBN 978-3-642-66777-0. Archived from the original on 30 March 2025. The second main component was d-isolysergic acid amide, or Iso-LA819 (No. 18a). After its identification in ololiuqui, trials were performed in man with oral doses up to 5 mg; they revealed central effects which were not LSD-like (ISBELL, 1962) but chiefly consisted in relaxation, synesthesias, and altered time experience (HEIMANN, 1965; HElM et al., 1968). [...] Table 2. Psychotomimetic activity and some pharmacodynamic effects of structural analogues of LSD [...]
^ ^a ^b ^c Chen W, De Wit-Bos L (2020). Risk assessment of Argyreia nervosa (PDF) (Report). doi:10.21945/rivm-2019-0210. A. nervosa contains ergot alkaloids, with D-lysergic acid amide (LSA) or ergine and its epimer iso-LSA or isoergine as main active components (see Chapter 3). [...] Human volunteer studies [...] Heim, Heimann & Lukács (1968) conducted experiments with increasing doses of LSA (0.04 or 0.09 mg/kg bw [3–6 mg total]), iso-LSA (0.03, 0.06 or 0.07 mg/kg bw [2–5 mg total]), or total alkaloids from the drug Ololiuqui (Rivea corymbosa; 0.02, 0.06, 0.08 or 0.10 mg/kg bw) in healthy volunteers. [...] Ingestion of LSA led to nausea, vomiting, an illness-like state with general fatigue, sweating and dizziness, vision problems, slower movements and speech (a state of lethargy and apathy), beginning approximately 45 minutes after ingestion and becoming more pronounced over the next hours. [...] Based on these results, the authors suggest that the vegetative symptoms are probably caused by LSA while iso-LSA leads to impairment of the thinking ability and effects on a persons' conscious (Heim, Heimann & Lukács, 1968). [...] Heim, E., Heimann, H., & Lukács, G., Die psychische Wirkung der mexikanischen Droge „Ololiuqui" am Menschen. Psychopharmacologia, 1968. 13(1): p. 35-48. doi:10.1007/BF00401617
^ ^a ^b ^c Shulgin AT (1976). "Psychotomimetic Agents". In Gordon M (ed.). Psychopharmacological Agents: Use, Misuse and Abuse. Medicinal Chemistry: A Series of Monographs. Vol. 4. Academic Press. pp. 59–146. doi:10.1016/b978-0-12-290559-9.50011-9. ISBN 978-0-12-290559-9. TABLE II RANGES OF ALKALOIDS FOUND IN SEVERAL PLANT PRODUCTSa [...] Only a few limited pharmacological studies have been made on the individual drugs. [...] Conditioned avoidance studies with isoergine in the rat (Vogel et al., 1972) support its role as a psychoactive agent. [...] Hofmann (1963a) has described the action of isoergine in man. Following the administration of 2.0 mg orally, there was a feeling of mental emptiness and unreality, but no indication of specific sensory distortion. [...] It appears that the agents that are responsible for the human activity of these plants are ergine and isoergine, and possibly the corresponding α-hydroxyethylamides of lysergic acid which could serve as metabolic precursors.
^ ^a ^b ^c Shulgin A. "#26. LSD-25". TiHKAL. Erowid.org. Retrieved 2012-02-03. LA-111, ergine, d-lysergamide. This is an active compound and has been established as a major component in morning glory seeds. It was assayed for human activity, by Albert Hofmann in self-trials back in 1947, well before this was known to be a natural compound. An i.m. administration of a 500 microgram dose led to a tired, dreamy state with an inability to maintain clear thoughts. After a short period of sleep, the effects were gone and normal baseline was recovered within five hours. Other observers have confirmed this clouding of consciousness leading to sleep. The epimer, inverted at C-8, is isoergine or d-isolysergamide, and is also a component of morning glory seeds. Hofmann tried a 2 milligram dose of this amide, and as with ergine, he experienced nothing but tiredness, apathy, and a feeling of emptiness. Both compounds are probably correctly dismissed as not being a contributor to the action of these seeds. It is important to note that ergine, as well as lysergic acid itself, is listed as a Schedule III drug in the Controlled Substances Act, as a depressant. This is, in all probability, a stratagem to control them as logical precursors to LSD.
^ ^a ^b Shulgin AT (1980). "Hallucinogens". In Burger A, Wolf ME (eds.). Burger's Medicinal Chemistry. Vol. 3 (4 ed.). New York: Wiley. pp. 1109–1137. ISBN 978-0-471-01572-7. OCLC 219960627. The alkaloid composition of these seeds is a fraction of a percent of their dry weight, but is made up largely of lysergic acid amide (60.34o) and the epimer isoergine (60.35). [...] The structures of the D ring portion of these several ergot-like alkaloids are illustrated, and the relative composition of the various morning glory seeds are listed in Table 60.5 [...] Table 60.5 Modifications of LSD [...] Human studies on ergine (60.34o) (150-152) and isoergine (60.35) (150) would indicate that these two alkaloids may account for much of the effects of the total seed, either directly or via the hydroxyethylamide precursors.
^ Shulgin AT (1972). "Hallucinogens, CNS Stimulants, And Cannabis". In Mulé, SJ, Brill H (eds.). Chemical and Biological Aspects of Drug Dependence. CRC Press. pp. 163–176. doi:10.1201/9780429260629-16. ISBN 978-0-87819-011-9. The major alkaloids present were found to be ergine (d-Lysergic acid amide, Figure 2; R1, R2, R3 = H) and the enantiomorph isoergine (d-Isolysergic acid amide, identical with ergine, but with the opposite epimeric configuration on the carbon atom that carries the amide carbonyl group). These two compounds have been shown to have some activity in man, but it is possible that their presence in the natural seed as the extremely labile acetaldehyde condensates (the hydroxyethylamides) may explain the activity of the seed compared to the lack of activity of the ergot isolates.8 [...] 8. Hofmann, A., Teonanacatl and Ololiuqui, two ancient magic drugs of Mexico, Bull. Narc., 23, 3, 1971.
^ ^a ^b Hofmann A (1963). "The Active Principles of the Seeds of Rivea Corymbosa and Ipomoea Violacea". Botanical Museum Leaflets, Harvard University. 20 (6). Harvard University Herbaria: 194–212. doi:10.5962/p.168542. ISSN 0006-8098. JSTOR 41762231. [...] chanoclavine, which has no outstanding pharmacological activity, appears to play no part in the occurrence of the psychic effects of badoh and badoh negro.
^ Cite error: The named reference HeimHeimannLukács1968 was invoked but never defined (see the help page).

[BrimblecombePinder1975-1] Brimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. OL 4850660M. d-Lysergic acid amide (ergine) is the major constituent of the seeds of both Rivea corymbosa and Ipomoea violacea, together with smaller amounts of d-isolysergic acid amide (isoergine), chanoclavine, elymoclavine, and the N-(1-hydroxyethyl)amides of lysergic and isolysergic acids. [...] Lysergol is found in Rivea but not in Ipomoea, while ergometrine (ergonovine) is present in the latter but not the former (Hofmann and Tscherter, 1960; Hofmann, 1961b, 1964; Hofmann and Cerletti, 1961; Greger, 1963). [...] The constituents of these convolvulaceous plants were not new even in 1960; the isomeric lysergic acid amides had previously been obtained as cleavage products by hydrolysis of the ergot alkaloids (Smith and Timmis, 1932, 1936), [...] the isomeric amides had also been synthesized in the laboratories of the Sandoz group (Stoll, Hofmann, and Schlientz, 1949). It is clear that the pharmacologically active constituents of ololiuqui are the isomeric lysergic acid amides. [...] Oral doses of 2 mg. of isolysergic acid amide are reported to produce a feeling of mental emptiness and total detachment from the outside world. Heim and his colleagues suggest that the overall effects of ololiuqui are due to these two compounds, the d-lysergic acid amide giving intoxication with strong autonomic side-effects and the d-isolysergic acid amide producing some euphoria, synaesthesia, and altered time experience. Certainly elymoclavine, lysergol, chanoclavine, and ergometrine produce no psychic changes in man (Isbell and Gorodetzky, 1966; Hofmann, 1968), though the first two do produce central excitation in animals (Yui and Takeo, 1958). Moreover, the time-course of absorption and distribution of d-isolysergic acid amide in rat brain exactly paralleled the course of behavioural aberrations produced by intraperitoneal doses of 5 mg./kg. (Vogel, Carapellotti, Evans, and Der Marderosian, 1972). [...] Five-hundred seeds of certain ornamental Ipomoea varieties contain as much as 1 mg. of ergometrine, which is usually considered to be an effective oxytocic in doses as low as 0·2-0·5 mg.

[Fanchamps1978-2] Fanchamps A (1978). "Some Compounds With Hallucinogenic Activity". In Berde B, Schild HO (eds.). Ergot Alkaloids and Related Compounds. Handbook of Experimental Pharmacology (HEP). Vol. 49. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 567–614. doi:10.1007/978-3-642-66775-6_8. ISBN 978-3-642-66777-0. Archived from the original on 30 March 2025. The second main component was d-isolysergic acid amide, or Iso-LA819 (No. 18a). After its identification in ololiuqui, trials were performed in man with oral doses up to 5 mg; they revealed central effects which were not LSD-like (ISBELL, 1962) but chiefly consisted in relaxation, synesthesias, and altered time experience (HEIMANN, 1965; HElM et al., 1968). [...] Table 2. Psychotomimetic activity and some pharmacodynamic effects of structural analogues of LSD [...]

[ChenDeWitBos2020-3] Chen W, De Wit-Bos L (2020). Risk assessment of Argyreia nervosa (PDF) (Report). doi:10.21945/rivm-2019-0210. A. nervosa contains ergot alkaloids, with D-lysergic acid amide (LSA) or ergine and its epimer iso-LSA or isoergine as main active components (see Chapter 3). [...] Human volunteer studies [...] Heim, Heimann & Lukács (1968) conducted experiments with increasing doses of LSA (0.04 or 0.09 mg/kg bw [3–6 mg total]), iso-LSA (0.03, 0.06 or 0.07 mg/kg bw [2–5 mg total]), or total alkaloids from the drug Ololiuqui (Rivea corymbosa; 0.02, 0.06, 0.08 or 0.10 mg/kg bw) in healthy volunteers. [...] Ingestion of LSA led to nausea, vomiting, an illness-like state with general fatigue, sweating and dizziness, vision problems, slower movements and speech (a state of lethargy and apathy), beginning approximately 45 minutes after ingestion and becoming more pronounced over the next hours. [...] Based on these results, the authors suggest that the vegetative symptoms are probably caused by LSA while iso-LSA leads to impairment of the thinking ability and effects on a persons' conscious (Heim, Heimann & Lukács, 1968). [...] Heim, E., Heimann, H., & Lukács, G., Die psychische Wirkung der mexikanischen Droge „Ololiuqui" am Menschen. Psychopharmacologia, 1968. 13(1): p. 35-48. doi:10.1007/BF00401617

[Shulgin1976-4] Shulgin AT (1976). "Psychotomimetic Agents". In Gordon M (ed.). Psychopharmacological Agents: Use, Misuse and Abuse. Medicinal Chemistry: A Series of Monographs. Vol. 4. Academic Press. pp. 59–146. doi:10.1016/b978-0-12-290559-9.50011-9. ISBN 978-0-12-290559-9. TABLE II RANGES OF ALKALOIDS FOUND IN SEVERAL PLANT PRODUCTSa [...] Only a few limited pharmacological studies have been made on the individual drugs. [...] Conditioned avoidance studies with isoergine in the rat (Vogel et al., 1972) support its role as a psychoactive agent. [...] Hofmann (1963a) has described the action of isoergine in man. Following the administration of 2.0 mg orally, there was a feeling of mental emptiness and unreality, but no indication of specific sensory distortion. [...] It appears that the agents that are responsible for the human activity of these plants are ergine and isoergine, and possibly the corresponding α-hydroxyethylamides of lysergic acid which could serve as metabolic precursors.

[TiHKAL-LSD-5] Shulgin A. "#26. LSD-25". TiHKAL. Erowid.org. Retrieved 2012-02-03. LA-111, ergine, d-lysergamide. This is an active compound and has been established as a major component in morning glory seeds. It was assayed for human activity, by Albert Hofmann in self-trials back in 1947, well before this was known to be a natural compound. An i.m. administration of a 500 microgram dose led to a tired, dreamy state with an inability to maintain clear thoughts. After a short period of sleep, the effects were gone and normal baseline was recovered within five hours. Other observers have confirmed this clouding of consciousness leading to sleep. The epimer, inverted at C-8, is isoergine or d-isolysergamide, and is also a component of morning glory seeds. Hofmann tried a 2 milligram dose of this amide, and as with ergine, he experienced nothing but tiredness, apathy, and a feeling of emptiness. Both compounds are probably correctly dismissed as not being a contributor to the action of these seeds. It is important to note that ergine, as well as lysergic acid itself, is listed as a Schedule III drug in the Controlled Substances Act, as a depressant. This is, in all probability, a stratagem to control them as logical precursors to LSD.

[Shulgin1980-6] Shulgin AT (1980). "Hallucinogens". In Burger A, Wolf ME (eds.). Burger's Medicinal Chemistry. Vol. 3 (4 ed.). New York: Wiley. pp. 1109–1137. ISBN 978-0-471-01572-7. OCLC 219960627. The alkaloid composition of these seeds is a fraction of a percent of their dry weight, but is made up largely of lysergic acid amide (60.34o) and the epimer isoergine (60.35). [...] The structures of the D ring portion of these several ergot-like alkaloids are illustrated, and the relative composition of the various morning glory seeds are listed in Table 60.5 [...] Table 60.5 Modifications of LSD [...] Human studies on ergine (60.34o) (150-152) and isoergine (60.35) (150) would indicate that these two alkaloids may account for much of the effects of the total seed, either directly or via the hydroxyethylamide precursors.

[Shulgin1972-7] Shulgin AT (1972). "Hallucinogens, CNS Stimulants, And Cannabis". In Mulé, SJ, Brill H (eds.). Chemical and Biological Aspects of Drug Dependence. CRC Press. pp. 163–176. doi:10.1201/9780429260629-16. ISBN 978-0-87819-011-9. The major alkaloids present were found to be ergine (d-Lysergic acid amide, Figure 2; R1, R2, R3 = H) and the enantiomorph isoergine (d-Isolysergic acid amide, identical with ergine, but with the opposite epimeric configuration on the carbon atom that carries the amide carbonyl group). These two compounds have been shown to have some activity in man, but it is possible that their presence in the natural seed as the extremely labile acetaldehyde condensates (the hydroxyethylamides) may explain the activity of the seed compared to the lack of activity of the ergot isolates.8 [...] 8. Hofmann, A., Teonanacatl and Ololiuqui, two ancient magic drugs of Mexico, Bull. Narc., 23, 3, 1971.

[Hofmann1963-8] Hofmann A (1963). "The Active Principles of the Seeds of Rivea Corymbosa and Ipomoea Violacea". Botanical Museum Leaflets, Harvard University. 20 (6). Harvard University Herbaria: 194–212. doi:10.5962/p.168542. ISSN 0006-8098. JSTOR 41762231. [...] chanoclavine, which has no outstanding pharmacological activity, appears to play no part in the occurrence of the psychic effects of badoh and badoh negro.

[HeimHeimannLukács1968-9] Cite error: The named reference HeimHeimannLukács1968 was invoked but never defined (see the help page).

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