Ergoline

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Ergoline
Ergoline Structural Formulae V.1.svg
3D ergoline molecule animation.gif
Clinical data
ATC code
  • none
Identifiers
  • (6aR)-4,6,6a,7,8,9,10,10a-Octahydroindolo[4,3-fg]quinoline
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
Formula C14H16N2
Molar mass 212.296 g·mol−1
3D model (JSmol)
  • [H][C@@]34Cc1c[nH]c2cccc(c12)[C@@]3([H])CCCN4
  • InChI=1S/C14H16N2/c1-3-11-10-4-2-6-15-13(10)7-9-8-16-12(5-1)14(9)11/h1,3,5,8,10,13,15-16H,2,4,6-7H2/t10-,13-/m1/s1 Yes check.svgY
  • Key:RHGUXDUPXYFCTE-ZWNOBZJWSA-N Yes check.svgY
   (verify)

Ergoline is a core structure in many alkaloids and their synthetic derivatives. Ergoline alkaloids were first characterized in ergot. Some of these are implicated in the condition of ergotism, which can take a convulsive form [1] or a gangrenous form. Even so, many ergoline alkaloids have been found to be clinically useful. Annual world production of ergot alkaloids has been estimated at 5,000–8,000 kg of all ergopeptines and 10,000–15,000 kg of lysergic acid, used primarily in the manufacture of semi-synthetic derivatives. [2]

Contents

Others, such as lysergic acid diethylamide, better known as LSD, a semi-synthetic derivative, and ergine, a natural derivative found in Argyreia nervosa , Ipomoea tricolor and related species, are known psychedelic substances. [3]

Natural occurrence

Ergoline alkaloids are found in fungi such as Claviceps purpurea, Claviceps paspali, [4] [5] and the related Periglandula, which have a permanent, symbiotic bond with numerous flowering vines, most notably, Turbina corymbosa and Ipomoea tricolor (“morning glory”). [6] Ergolines are concentrated in the seeds, [7] which have been used for ages by indigenous central/south Americans [8] (i.e. T. corymbosa seeds are known as ololiuhqui [9] [10] ) The principal alkaloids in the seeds appear to be ergine and isoergine, but they're just decomposition products of lysergic acid hydroxyethylamide, isolysergic hydroxyethylamide, lysergic acid hydroxymethylethylamide (syn. ergonovine), and isolysergic acid hydroxymethylethylamide (syn. ergonovinine). [11] [12] [13] [14] [15] [16] [17] All of the other ergolines have been quantified in very small amts. except for penniclavine, which was found to be the predominant ergoline in a 2016 assay of I. tricolor seeds. [18] Ergolines have been identified in 42 Morning Glory species. [19] The only ergolines of these seeds that have been trialed as isolates are ergine, ergonovine, and lysergol, with lysergol showing the weakest effect [20] (refs: Ergine / Psychedelic Effects, Ergometrine / Psychedelic Effects).

History

Ergoline alkaloids were first isolated from ergot, a fungus that infects rye and causes ergotism or St. Anthony's fire. [21] Reports of the toxic effects due to ergoline alkaloids date back to the 12th century. [22] Ergot also has a long history of medicinal use, which led to attempts to characterize its activity chemically. First reports of its use date back to 1582, where preparations of ergot were used in small doses by midwives to induce strong uterine contractions. [2] [22] The first use of ergoline alkaloids in modern medicine was described in 1808 by John Stearns, an American physician, who had reported on the uterine contractile actions of a preparation of ergot as a remedy for "quickening birth". [2]

Attempts to characterize the activity of ergoline alkaloids began in 1907, with the isolation of ergotoxine by G. Barger and F. H. Carrin. [23] However, the industrial production of ergot alkaloids didn't begin until 1918, when Arthur Stoll patented the isolation of ergotamine tartrate, which was marketed by Sandoz in 1921. Following the determination of the basic chemical structure of the ergot alkaloids in 1930, an era of intensive exploration of synthetic derivatives began and industrial production of ergoline alkaloids exploded, with Sandoz continuing to be the leading company in their production worldwide, up until 1950 when other competitors arose. [2] [23] The company, now renamed Novartis, still retains its leadership in the product of ergot alkaloids. In 1943, Arthur Stoll and Albert Hofmann reported the first total synthesis of an ergot alkaloid, ergometrine. [24] Though the synthesis found no industrial application, this was a huge leap forward in the industry.

Uses

There are a variety of clinically useful ergoline derivatives for the purpose of vasoconstriction, the treatment of migraines, and treatment of Parkinson's disease. Ergoline alkaloids found their place in pharmacology long before modern medicine as preparations of ergot were often used by midwives in the 12th century to stimulate childbirth. [25] Following Arthur Stoll's isolation of ergometrine, the therapeutic use of ergoline derivatives became well explored.

The induction of uterine contractions via the preparation of ergot was attributed to ergonovine, an ergoline derivative found in ergot, which is a powerful oxytocic. From this, methergine, a synthetic derivative, was elucidated. [22] While used to facilitate child birth, ergoline derivatives can pass into breast milk and should not be used during breastfeeding. [26] They are uterine contractors that can increase the risk of miscarriage during pregnancy. [9]

Another example of medically relevant ergoline alkaloids is ergotamine, an alkaloid also found in ergot. It acts as a vasoconstrictor and has been reported to control migraines. From ergotamine, the anti-migraine drugs dihydroergotamine and methysergide were developed by Albert Hofmann. [27]

Ergoline derivatives, such as hydergine, a mixture of dihydroergotoxine mesylates or ergoline mesylates, have also been used in the treatment of dementia. The use of these alkaloids in the treatment of Parkinson's disease has also been prominent. Drugs such as bromocriptine act as a dopamine receptor agonist, stimulating the nerves that control movement. [28] Newer synthetic ergoline derivatives that have been synthesized for the treatment of Parkinson's disease include pergolide and lisuride, which both act as dopamine agonists as well. [28]

A famous ergoline derivative is the psychedelic drug LSD, a semi-synthetic ergoline alkaloid that was discovered by Albert Hofmann. LSD is considered a Schedule I controlled substance. Ergometrine and ergotamine are included as schedule I precursors in the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. [29]

Mechanism of action

The mechanism of ergoline alkaloids varies for each derivative. A variety of modifications can be made to the ergoline skeleton to produce medically relevant derivatives. Types of potential ergoline-based drugs include dopaminergic, antidopaminergic, serotonergic, and antiserotonergic. [30] Ergoline alkaloids often interfere with multiple receptor sites, leading to negative side effects and adding to the challenge of drug development.

Dopaminergic/antidopaminergic

Ergolines, such as ergotoxin, have been reported to inhibit the deciduoma reaction, which is reversed through injection of progesterone. Thus, it was concluded that ergotoxin, and related ergolines, act via the hypothalamus and pituitary gland to inhibit the secretion of prolactin. [30] Drugs such as bromocriptine interact with the dopaminergic receptor sites as agonists with selectivity for D2 receptors, making them effective in treating Parkinson's disease. While the part of the ergoline alkaloid structure responsible for dopaminergic properties has yet to be identified, some reason that it is due to the pyroleethylamine moiety while others assert that it is due to the indoleethylamine partial structure. [30]

Antidopaminergic ergolines have found use in antiemetics and in the treatment of schizophrenia. These substances are neuroleptic and are either an antagonist of dopamine at the postsynaptic level at the D2 receptor site or an agonist of dopamine at the presynaptic level at the D1 receptor site. [30] The antagonist or agonist behavior of the ergolines are substrate dependent and mixed agonist/antagonist behaviors of ergoline derivatives have been reported. [30]

Serotonergic/antiserotonergic

The primary challenges of developing serotonergic/antiserotonergic ergolines is attributed to serotonin, or 5-HT, acting on various distinct receptor sites. Similarly, ergoline alkaloids have been shown to exhibit both 5-HT agonist and antagonist behaviors for multiple receptors, such as metergoline, a 5-HT1A agonist/5-HT2A antagonist, and mesulergine, a 5-HT2A/2C antagonist. [30] The selectivity and affinity of ergolines for certain 5-HT receptors can be improved by introducing a bulky group on the phenyl ring of the ergoline skeleton, which would prevent the interaction of ergoline derivatives with receptors. [30] This methodology has been used to develop selective 5-HT1A and 5-HT2A ergolines in particular.

Ergoline derivatives

There are 3 main classes of ergoline derivatives, the water-soluble amides of lysergic acid , the water-insoluble ergopeptines (i.e., ergopeptides ), and the clavine group. [31]

Lysergic acid amides

The relationship between these compounds is summarized in the following structural formula and table of substitutions.

Substituted ergine (structural formula) Ergine - Ergines.svg
Substituted ergine (structural formula)
NameR1R2R3
Ergine HHH
Ergonovine HCH(CH3)CH2OHH
Methergine HCH(CH2CH3)CH2OHH
Methysergide CH3 CH(CH2CH3)CH2OHH
LSD H CH2CH3 CH2CH3

Peptide alkaloids

Peptide ergot alkaloids or ergopeptines (also known as ergopeptides) are ergoline derivatives that contain a tripeptide structure attached to the basic ergoline ring in the same location as the amide group of the lysergic acid derivatives. This structure consists of proline and two other α-amino acids, linked in an unusual cyclol formation >N-C(OH)< with the carboxyl carbon of proline, at the juncture between the two lactam rings. [32] Some of the important ergopeptines are summarized below. [33] In addition to the following ergopeptines, a commonly encountered term is ergotoxine, which refers to a mixture of equal proportions of ergocristine, ergocornine and ergocryptine, the latter being a 2:1 mixture of alpha - and beta-ergocryptine. Ergopeptines are considered to be the most toxic and are capable of inducing gangrene: “The low molecular ergolines are lacking the complex peptide moiety, which is apparently responsible for the persistence of the ergopeptines at the receptor molecules.” [34]

Ergopeptides (structural formula) Ergopeptine - Ergopeptines.svg
Ergopeptides (structural formula)
NameR1R2R3Amino acid at R2Amino acid at R3
Ergocristine CH(CH3)2 benzyl Valine Phenylalanine
Ergocornine CH(CH3)2CH(CH3)2Valine Valine
alpha-Ergocryptine CH(CH3)2CH2CH(CH3)2Valine Leucine
beta-Ergocryptine CH(CH3)2CH(CH3)CH2CH3 (S)Valine Isoleucine
Ergotamine CH3 benzyl Alanine Phenylalanine
Ergovaline CH3CH(CH3)2AlanineValine
alpha-Ergosine CH3CH2CH(CH3)2AlanineLeucine
beta-Ergosine CH3CH(CH3)CH2CH3 (S)AlanineIsoleucine
Bromocriptine (semisynthetic) Br CH(CH3)2CH2CH(CH3)2ValineLeucine

Clavines

A variety of modifications to the basic ergoline are seen in nature, for example agroclavine, elymoclavine, lysergol. Those deriving from dimethylergoline are referred to as clavines. Examples of clavines, include festuclavine, fumigaclavine A, fumigaclavine B and fumigaclavine C.

Others

Some synthetic ergoline derivatives do not fall easily into any of the above groups. Some examples are:

See also

Related Research Articles

<i>Ipomoea corymbosa</i> Species of plant

Ipomoea corymbosa is a species of morning glory, native throughout Latin America from Mexico as far south as Peru and widely naturalised elsewhere. Its common names include Christmasvine, Christmaspops, and snakeplant.

<span class="mw-page-title-main">Ergot</span> Group of fungi of the genus Claviceps

Ergot or ergot fungi refers to a group of fungi of the genus Claviceps.

<span class="mw-page-title-main">Ergine</span> Chemical compound

Ergine, also known as lysergic acid amide and lysergamide, is an ergoline alkaloid that occurs in various species of vines of the Convolvulaceae and some species of fungi. The psychedelic properties in the seeds of ololiuhqui, Hawaiian baby woodrose and morning glories have been linked to ergine and/or isoergine, its epimer, as it is an alkaloid present in the seeds.

<span class="mw-page-title-main">Lysergic acid</span> Precursor for a range of ergoline alkaloids produced by the ergot fungus

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 Turbina corymbosa (ololiuhqui), Argyreia nervosa, and Ipomoea tricolor.

<span class="mw-page-title-main">Ergotamine</span> Chemical compound in the ergot family of alkaloids

Ergotamine, sold under the brand name Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It is structurally similar to several neurotransmitters, and it acts as a vasoconstrictor. It is used for acute migraines, sometimes with caffeine as the combination ergotamine/caffeine.

<i>Ipomoea tricolor</i> Species of plant

Ipomoea tricolor, the Mexican morning glory or just morning glory, is a species of flowering plant in the family Convolvulaceae, native to the tropics of the Americas, and widely cultivated and naturalised elsewhere.

<span class="mw-page-title-main">Ergoloid</span> Chemical compound

Ergoloid mesylates (USAN), co-dergocrine mesilate (BAN) or dihydroergotoxine mesylate, trade name Hydergine, is a mixture of the methanesulfonate salts of three dihydrogenated ergot alkaloids.

<i>Argyreia nervosa</i> Species of plant

Argyreia nervosa is a perennial climbing vine native to the Indian subcontinent and introduced to numerous areas worldwide, including Hawaii, Africa, and the Caribbean. Though it can be invasive, it is often prized for its aesthetic and medicinal value. Common names include Hawaiian baby woodrose, adhoguda अधोगुडा or vidhara विधारा (Sanskrit), elephant creeper and woolly morning glory. Its seeds are known for their powerful entheogenic properties, greater or similar to those of Ipomoea species, with users reporting significant psychedelic and spiritual experiences. The two botanical varieties are Argyreia nervosa var. nervosa described here, and Argyreia nervosa var. speciosa, the roots of which are used in Ayurvedic medicine.

<span class="mw-page-title-main">Psilocin</span> Chemical compound

Psilocin, also known as 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin. Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. Acting on the serotonin 5-HT2A receptors, psilocin's psychedelic effects are directly correlated with the drug's occupancy at these receptor sites. The subjective mind-altering effects of psilocin are highly variable and are said to resemble those of lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT).

The Misuse of Drugs Act 1973 is a statute of the Parliament of Singapore that enables authorities to prosecute offenders for crimes involving illegal drugs. The law is designed specifically to grant the Government of Singapore, through its agencies such as the Central Narcotics Bureau, enforcement powers to combat offences such as the trafficking, importation or exportation, possession, and consumption of controlled drugs.

<span class="mw-page-title-main">Lysergamides</span> Class of chemical compounds

Amides of lysergic acid are collectively known as lysergamides or ergoamides, 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.

<span class="mw-page-title-main">Ergonovine</span> Lysergamide

Ergonovine, also known as ergometrine and lysergic acid propanolamide is a medication used to cause contractions of the uterus to treat heavy vaginal bleeding after childbirth. It can be used either by mouth, by injection into a muscle, or injection into a vein. It begins working within 15 minutes when taken by mouth and is faster in onset when used by injection. Effects last between 45 and 180 minutes.

<span class="mw-page-title-main">Dihydroergotamine</span> Chemical used to treat migraines

Dihydroergotamine (DHE), sold under the brand names D.H.E. 45 and Migranal among others, is an ergot alkaloid used to treat migraines. It is a derivative of ergotamine. It is administered as a nasal spray or injection and has an efficacy similar to that of sumatriptan. Nausea is a common side effect.

<span class="mw-page-title-main">Lysergic acid hydroxyethylamide</span> Chemical compound

ᴅ-Lysergic acid α-hydroxyethylamide, also known as ᴅ-lysergic acid methyl carbinolamide, is an ergoamide and an ergoline. It is perhaps the main constituent of the parasitic fungus, Claviceps paspali; and found in trace amounts in Claviceps Purpurea. C. paspali and C. purpurea are ergot-spreading fungi. Periglandula, Clavicipitacepus fungi, are permanently symbiotically connected to an estimated 450 species of Convolvulaceae and thus generate LAH in some of them. The most well-known ones are Ipomoea tricolor, Turbina corymbosa (coaxihuitl), and Argyreia nervosa.

<span class="mw-page-title-main">Methylergometrine</span> Chemical compound

Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and as an antimigraine agent in the treatment of migraine headaches. It reportedly produces psychedelic effects similar to those of lysergic acid diethylamide (LSD) at high doses.

<span class="mw-page-title-main">Dopamine agonist</span> Compound that activates dopamine receptors

A dopamine agonist is a compound that activates dopamine receptors. There are two families of dopamine receptors, D1-like and D2-like. They are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. Dopamine agonists are primarily used in the treatment of the motor symptoms of Parkinson's disease, and to a lesser extent, in hyperprolactinemia and restless legs syndrome. They are also used off-label in the treatment of clinical depression. Impulse control disorders are associated with the use of dopamine agonists for whatever condition.

<span class="mw-page-title-main">Indole alkaloid</span> Class of alkaloids

Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known different compounds, it is one of the largest classes of alkaloids. Many of them possess significant physiological activity and some of them are used in medicine. The amino acid tryptophan is the biochemical precursor of indole alkaloids.

<span class="mw-page-title-main">Nicergoline</span> Chemical compound

Nicergoline, sold under the brand name Sermion among others, is an ergot derivative used to treat senile dementia and other disorders with vascular origins. Internationally it has been used for frontotemporal dementia as well as early onset in Lewy body dementia and Parkinson's dementia. It decreases vascular resistance and increases arterial blood flow in the brain, improving the utilization of oxygen and glucose by brain cells. It has similar vasoactive properties in other areas of the body, particularly the lungs. Unlike many other ergolines, such as ergotamine, nicergoline is not associated with cardiac fibrosis.

<span class="mw-page-title-main">LSD-Pip</span> Compound related to LSD

LSD-Pip is a compound from the ergoline family, related to LSD but with the N,N-diethyl substitution replaced by a piperidine group. It is more potent than the corresponding pyrrolidine and morpholine analogues, but is still several times less potent than LSD as a 5-HT2A agonist. Early studies suggested this compound to be inactive as a psychedelic in humans, though this does not seem to have been confirmed by any more recent work.

<span class="mw-page-title-main">Lysergine</span> Ergot alkaloid and serotonin receptor agonist

Lysergine, also known as 9,10-didehydro-6,8β-dimethylergoline, is an ergot alkaloid and serotonin receptor agonist of the ergoline family. It is a minor constituent of ergot.

References

  1. ↑ Schardl CL, Panaccione DG, Tudzynski P (2006). "Ergot alkaloids--biology and molecular biology". The Alkaloids. Chemistry and Biology. 63. Elsevier: 45–86. doi:10.1016/s1099-4831(06)63002-2. ISBN   978-0-12-469563-4. PMID   17133714.
    "Clavines are thought to contribute substantially to convulsive ergotism, since C. fusiformis ergots, which possess clavines, but no [lysergic acid] or lysergyl amides, cause convulsive symptoms (26). However, the ergopeptines are known to produce similar symptoms, and are also thought to cause gangrenous ergotism (6). The occurrence of convulsive ergotism without dry gangrene suggests that other clavine or lysergyl alkaloids are involved, or that individual effects of specific ergopeptines may give clinically different syndromes (6)."
    II. Through the Ages: A History of Ergot Alkaloid Use, Abuse, and Poisoning, p. 50
  2. 1 2 3 4 Schiff PL (October 2006). "Ergot and its alkaloids". American Journal of Pharmaceutical Education. 70 (5): 98. doi:10.5688/aj700598. PMC   1637017 . PMID   17149427.
  3. ↑ Juszczak GR, Swiergiel AH (2013). "Recreational use of D-lysergamide from the seeds of Argyreia nervosa, Ipomoea tricolor, Ipomoea violacea, and Ipomoea purpurea in Poland". Journal of Psychoactive Drugs. 45 (1): 79–93. doi:10.1080/02791072.2013.763570. PMID   23662334. S2CID   22086799.
  4. ↑ Schultes R (1973). "4. Plants of Hallucinogenic Use / The Fungi". The Botany and Chemistry of Hallucinogens. Springfield, IL: Charles Thomas. p. 37. ISBN   9780398064167.
    "Whereas ergine, lysergic acid hydroxyethylamide, and lysergyl L-valine methylester occur in ergot of rye only in trace amounts, ergonovine (synonyms ergometrine, ergobasin), which is the specific oxytocic factor of a ergot, is often found in remarkable quantities. In contrast, ergine and hydroxyethylamide of lysergic acid are the main constituents of certain ergot growing on wild grasses, e.g. Paspalum distichum." 4. Plants of Hallucinogenic Use / The Fungi, p. 37
  5. ↑ Wasson RG, Hofmann A, Ruck CA, Webster P (November 25, 2008) [1978]. Forte R (ed.). The Road to Eleusis: Unveiling the Secret of the Mysteries (30th Anniversary ed.). Berkeley, Calif.: North Atlantic Books. ISBN   978-1-55643-752-6.
    "We analyzed ergot of wheat and ergot of barley in our laboratory and they were found to contain basically the same alkaloids as ergot of rye, viz. alkaloids of the ergotamine and ergotoxine group, ergonovine, and sometimes also traces of lysergic acid amide. As I said before, ergonovine and lysergic acid amide, both psychoactive, are soluble in water whereas the other alkaloids are not." Albert Hofmann, 2. A Challenging Question and my Answer, p. 42
  6. ↑ Leistner E, Steiner U (February 3, 2018). "The Genus Periglandula and Its Symbiotum with Morning Glory Plants (Convolvulaceae)". In Anke T, Schüffler A (eds.). Physiology and Genetics. Cham: Springer International Publishing. pp. 131–147. doi:10.1007/978-3-319-71740-1_5. ISBN   978-3-319-71739-5 . Retrieved 2024-11-21.
  7. ↑ Nowak J, Woźniakiewicz M, Klepacki P, Sowa A, Kościelniak P (May 2016). "Identification and determination of ergot alkaloids in Morning Glory cultivars". Analytical and Bioanalytical Chemistry. 408 (12): 3093–3102. doi:10.1007/s00216-016-9322-5. PMC   4830885 . PMID   26873205.
    "ergine and ergometrine concentration is 12-fold lower in plant samples than in seeds." Analysis of IP-HB2 young plants
  8. ↑ Ruck CA (2006). Sacred Mushrooms of the Goddess: The Secrets of Eleusis. Berkeley, California: Ronin Publishing, Inc. ISBN   978-1-57951-030-5.
    "Ololiuhqui was far more prominent as an entheogen here in Mesoamerica than those mushrooms; the mushrooms are mentioned only here and there by a few competent chroniclers; yet almost an entire book was devoted to denouncing mainly the ololiuhqui idolatry. The annals of the Inquisition contain many times more autos de fe for ololiuhqui than for mushrooms." Jonathan Ott, quoted in 15. Mixing the Kykeon Anew (section: Ergine)
  9. 1 2 Schardl CL, Panaccione DG, Tudzynski P (2006). Ergot alkaloids – biology and molecular biology. The Alkaloids: Chemistry and Biology. Vol. 63. pp. 45–86. doi:10.1016/S1099-4831(06)63002-2. ISBN   978-0-12-469563-4. PMID   17133714.
  10. ↑ Carod-Artal FJ (2015). "Hallucinogenic drugs in pre-Columbian Mesoamerican cultures". Neurologia. 30 (1): 42–49. doi: 10.1016/j.nrl.2011.07.003 . PMID   21893367.
  11. ↑ Shulgin A (2012-12-02) [1976]. "4. Psychotomimetic Agents". In Maxwell G (ed.). Psychopharmacological agents. Medicinal Chemistry. Vol. 4. New York: Academic Press. pp. 71–72. ISBN   978-0-12-290559-9.
    "These compounds, although well documented as components in the Convolvulaceae, are possibly lost in several of the analyses of alkaloid composition. They are extremely unstable, and are very readily degraded into acetaldehyde and the corresponding amide, ergine or isoergine." (p. 72)
  12. ↑ Schultes RE, Hofmann A (1973). The Botany and Chemistry of Hallucinogens. Springfield, IL: Charles Thomas. p. 246. ISBN   9780398064167.
    "Later, it was found that ergine and isoergine were present in the seeds to some extent in the form of lysergic acid N-(1-hydroxyethyl) amide and isolysergic acid N-(1-hydroxyethyl) amide, respectively, and that, during the isolation procedure, they easily hydrolize to ergine and isoergine, respectively, and acetaldehyde." 4. Plants of Hallucinogenic Use / Convolvulaceae, p. 246
  13. ↑ Flieger M, Sedmera P, Vokoun J, R̆ic̄icovā A, R̆ehác̆ek Z (1982-02-19). "Separation of four isomers of lysergic acid α-hydroxyethylamide by liquid chromatography and their spectroscopic identification". Journal of Chromatography A. 236 (2): 441–452. doi:10.1016/S0021-9673(00)84895-5. ISSN   0021-9673.
  14. ↑ Ramstad E (1968). "Chemistry of alkaloid formation in ergot". Lloydia. 31: 327–341.
  15. ↑ Kleinerová E, Kybal J (September 1973). "Ergot alkaloids. IV. Contribution to the biosynthesis of lysergic acid amides". Folia Microbiologica. 18 (5): 390–392. doi:10.1007/BF02875934. PMID   4757982.
  16. ↑ Panaccione DG, Tapper BA, Lane GA, Davies E, Fraser K (October 2003). "Biochemical outcome of blocking the ergot alkaloid pathway of a grass endophyte". Journal of Agricultural and Food Chemistry. 51 (22): 6429–6437. doi:10.1021/jf0346859. PMID   14558758.
  17. ↑ Panaccione DG (2010). "Ergot alkaloids". In Hofrichter M (ed.). The Mycota, Industrial Applications. Vol. 10 (2nd ed.). Berlin-Heidelburg, Germany: Springer-Verlag. pp. 195–214.
  18. ↑ Nowak J, Woźniakiewicz M, Klepacki P, Sowa A, Kościelniak P (May 2016). "Identification and determination of ergot alkaloids in Morning Glory cultivars". Analytical and Bioanalytical Chemistry. 408 (12) (published February 14, 2016): 3093–3102. doi:10.1007/s00216-016-9322-5. PMC   4830885 . PMID   26873205.
    See Table 3 under "Analysis of different Ipomoea seeds".
    Concentration values for "LSH", "Lyzergol/isobars", penniclavine, and chanoclavine can be obtained by dividing the concentration values of ergine or ergometrine by their relative abundance values and multiplying that number by the relative abundance value of the specified chemical.
  19. ↑ Eich E (January 12, 2008). "4.2 Ergolines". Solanaceae and convolvulaceae - secondary metabolites: biosynthesis, chemotaxonomy, biological and economic significance: a handbook. Berlin, Heidelberg: Springer-Verlag. doi:10.1007/978-3-540-74541-9. ISBN   978-3-540-74540-2. OCLC   195613136.
    Table 4.1 Unambiguously ergoline-positive Ipomoea species (pages 225-227)
    Table 4.4 Unambiguously ergoline-positive Argyreia species (p. 236)
    Table 4.5 Unambiguously ergoline-positive Stictocardia and Turbina species (p. 238)
  20. ↑ Heim E, Heimann H, Lukács G (1968). "Die psychische Wirkung der mexikanischen Droge "Ololiuqui" am Menschen". Psychopharmacologia (in German). 13 (1): 35–48. doi:10.1007/BF00401617. PMID   5675457
    c) ᴅ-Lysergol

    “Changes occurred only with a dosage of 8 mg, with a noticeable slowing of expression and behavior. The facial expression appeared flat, and speech showed a reduction in the five expressive qualities. Subjectively, fewer vegetative sensations were observed, but there was a marked inhibition of initiative.” 3. Results, p. 40
    Translated from German with ChatGPT.    {{cite journal}}: CS1 maint: postscript (link)
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  25. ↑ European Commission. Joint Research Centre. Report on the 2017 proficiency test of the European Union reference laboratory for mycotoxins determination of ergot alkaloids in rye. OCLC   1060942360.
  26. ↑ kidsgrowth.org --> Drugs and Other Substances in Breast Milk Archived 2007-06-23 at archive.today Retrieved on June 19, 2009.
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  33. ↑ Yates SG, Plattner RD, Garner GB (July 1985). "Detection of ergopeptine alkaloids in endophyte-infected, toxic Ky-31 tall fescue by mass spectrometry/mass spectrometry" (PDF). Journal of Agricultural and Food Chemistry. 33 (4): 719–722. doi:10.1021/jf00064a038.[ permanent dead link ]
  34. ↑ Eich E (January 12, 2008). "4.2 Ergolines". Solanaceae and convolvulaceae - secondary metabolites: biosynthesis, chemotaxonomy, biological and economic significance: a handbook. Berlin, Heidelberg: Springer-Verlag. doi:10.1007/978-3-540-74541-9. ISBN   978-3-540-74540-2. OCLC   195613136.
    "The low molecular ergolines are lacking the complex peptide moiety, which is apparently responsible for the persistence of the ergopeptines at the receptor molecules." 4.2.5.1 Mechanisms of Action and Therapeutic Relevance, p. 249
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