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{{Short description|Chemical compound}}
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'''Ergoline''' is a chemical compound whose structural skeleton is contained in a variety of [[alkaloid]]s, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being [[ergine]], were initially characterized in [[ergot]]. Some of these are implicated in the condition [[ergotism]], which can take a convulsive form 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&nbsp;kg of all ergopeptines and 10,000–15,000&nbsp;kg of [[lysergic acid]], used primarily in the manufacture of semi-synthetic derivatives.<ref name=":02">{{Cite journal|last=Schiff|first=Paul L.|date=September 2006|title=Ergot and Its Alkaloids|journal=American Journal of Pharmaceutical Education|language=en|volume=70|issue=5|pages=98|doi=10.5688/aj700598|issn=0002-9459|pmc=1637017|pmid=17149427}}</ref>
'''Ergoline''' is a chemical compound whose structural skeleton is contained in a variety of [[alkaloid]]s, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being [[ergine]], were initially characterized in [[ergot]]. Some of these are implicated in the condition [[ergotism]], which can take a convulsive form 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&nbsp;kg of all ergopeptines and 10,000–15,000&nbsp;kg of [[lysergic acid]], used primarily in the manufacture of semi-synthetic derivatives.<ref name=":02">{{cite journal | vauthors = Schiff PL | title = Ergot and its alkaloids | journal = American Journal of Pharmaceutical Education | volume = 70 | issue = 5 | pages = 98 | date = October 2006 | pmid = 17149427 | pmc = 1637017 | doi = 10.5688/aj700598 }}</ref>


Others, such as [[Lysergic acid diethylamide]], better known as LSD, a fully [[Organic compound#Synthetic compounds|synthetic]] derivative, and [[ergine]], an natural derivative found in ''[[Argyreia nervosa]]'', ''[[Ipomoea tricolor]]'' and related species, are known [[Psychedelic drug|psychedelic]] substances.<ref>{{cite journal|last1=Juszczak|first1=GR|last2=Swiergiel|first2=AH|year=2013|title=Recreational use of D-lysergamide from the seeds of Argyreia nervosa, Ipomoea tricolor, Ipomoea violacea, and Ipomoea purpurea in Poland|journal=J Psychoactive Drugs|volume=45|issue=1|pages=79–93|doi=10.1080/02791072.2013.763570|pmid=23662334}}</ref>
Others, such as [[lysergic acid diethylamide]], better known as LSD, a [[Semisynthesis|semi-synthetic]] derivative, and [[ergine]], a natural derivative found in ''[[Argyreia nervosa]]'', ''[[Ipomoea tricolor]]'' and related species, are known [[Psychedelic drug|psychedelic]] substances.<ref>{{cite journal | vauthors = Juszczak GR, Swiergiel AH | title = Recreational use of D-lysergamide from the seeds of Argyreia nervosa, Ipomoea tricolor, Ipomoea violacea, and Ipomoea purpurea in Poland | journal = Journal of Psychoactive Drugs | volume = 45 | issue = 1 | pages = 79–93 | year = 2013 | pmid = 23662334 | doi = 10.1080/02791072.2013.763570 | s2cid = 22086799 }}</ref>


==Natural occurrence==
==Natural occurrence==
Ergoline alkaloids are found in lower [[fungi]] and some species of [[flowering plant]]s: the [[Mexico|Mexican]] species ''[[Turbina corymbosa]]'' and ''[[Ipomoea tricolor]]'' of the [[Convolvulaceae]] (morning glory) family, the seeds of which were identified as the psychedelic plant drugs known as "ololiuhqui" and "tlitliltzin", respectively.<ref name="Schardl20063">{{cite journal|vauthors=Schardl CL, Panaccione DG, Tudzynski P|year=2006|title=Ergot alkaloids&nbsp;– biology and molecular biology|series=The Alkaloids: Chemistry and Biology|volume=63|pages=45–86|doi=10.1016/S1099-4831(06)63002-2|isbn=978-0-12-469563-4|pmid=17133714}}</ref><ref>{{cite journal|last=Carod-Artal|first=FJ|year=2015|title=Hallucinogenic drugs in pre-Columbian Mesoamerican cultures|url=http://www.elsevier.es/en-revista-neurologia-english-edition--495-pdf-S2173580814001527-S300|journal=Neurologia|volume=30|issue=1|pages=42–9|doi=10.1016/j.nrl.2011.07.003|pmid=21893367|doi-access=free}}</ref> The principal alkaloids in the seeds are ergine and its [[optical isomer]] isoergine, with several other lysergic acid derivatives and clavines present in lesser amounts. The [[Hawaii]]an species ''[[Argyreia nervosa]]'' includes similar alkaloids. It is possible, though not proven, that [[ergine]] or isoergine are responsible for the [[Psychedelic drug|psychedelic]] effects. There may be a fungal origin of the ergoline alkaloids also in the Convolvulaceae. Like the ergot alkaloids in some monocot plants, the ergoline alkaloids found in the plant ''[[Ipomoea asarifolia]]'' (Convolvulaceae) are produced by a seed-transmitted [[Endophyte|endophytic]] [[Clavicipitaceae|clavicipitaceous]] [[fungus]].<ref>{{cite journal|last1=Steiner|first1=U|last2=Ahimsa-Müller|first2=MA|last3=Markert|first3=A|last4=Kucht|first4=S|last5=Groß|first5=J|last6=Kauf|first6=N|last7=Kuzma|first7=M|last8=Zych|first8=M|last9=Lamshöft|first9=M|last10=Furmanowa|first10=M|last11=Knoop|first11=V|year=2006|title=Molecular characterization of a seed transmitted clavicipitaceous fungus occurring on dicotyledoneous plants (Convolvulaceae)|journal=Planta|volume=224|issue=3|pages=533–44|doi=10.1007/s00425-006-0241-0|pmid=16525783|last12=Drewke|first12=C|last13=Leistner|first13=E}}</ref>
Ergoline alkaloids are found in lower [[fungi]] and some species of [[flowering plant]]s: the [[Mexico|Mexican]] species ''[[Turbina corymbosa]]'' and ''[[Ipomoea tricolor]]'' of the [[Convolvulaceae]] (morning glory) family, the seeds of which were identified as the psychedelic plant drugs known as "ololiuhqui" and "tlitliltzin", respectively.<ref name="Schardl20063">{{cite book|vauthors=Schardl CL, Panaccione DG, Tudzynski P|year=2006|title=Ergot alkaloids&nbsp;– biology and molecular biology|series=The Alkaloids: Chemistry and Biology|volume=63|pages=45–86|doi=10.1016/S1099-4831(06)63002-2|isbn=978-0-12-469563-4|pmid=17133714}}</ref><ref>{{cite journal | vauthors = Carod-Artal FJ | title = Hallucinogenic drugs in pre-Columbian Mesoamerican cultures | journal = Neurologia | volume = 30 | issue = 1 | pages = 42–49 | year = 2015 | pmid = 21893367 | doi = 10.1016/j.nrl.2011.07.003 | doi-access = free }}</ref> The principal alkaloids in the seeds are ergine and its [[optical isomer]] isoergine, with several other lysergic acid derivatives and clavines present in lesser amounts. The [[Hawaii]]an species ''[[Argyreia nervosa]]'' includes similar alkaloids. It is possible, though not proven, that [[ergine]] or isoergine are responsible for the [[Psychedelic drug|psychedelic]] effects. There may be a fungal origin of the ergoline alkaloids also in the Convolvulaceae. Like the ergot alkaloids in some monocot plants, the ergoline alkaloids found in the plant ''[[Ipomoea asarifolia]]'' (Convolvulaceae) are produced by a seed-transmitted [[Endophyte|endophytic]] [[Clavicipitaceae|clavicipitaceous]] [[fungus]].<ref>{{cite journal | vauthors = Steiner U, Ahimsa-Müller MA, Markert A, Kucht S, Gross J, Kauf N, Kuzma M, Zych M, Lamshöft M, Furmanowa M, Knoop V, Drewke C, Leistner E | display-authors = 6 | title = Molecular characterization of a seed transmitted clavicipitaceous fungus occurring on dicotyledoneous plants (Convolvulaceae) | journal = Planta | volume = 224 | issue = 3 | pages = 533–544 | date = August 2006 | pmid = 16525783 | doi = 10.1007/s00425-006-0241-0 | s2cid = 25682792 }}</ref>


==History==
==History==
Ergoline [[alkaloid]]s were first isolated from [[ergot]], a fungus that infects rye and causes [[ergotism]] or St. Anthony's fire.<ref>{{Cite journal|last=Gerhards|first=Nina|last2=Neubauer|first2=Lisa|last3=Tudzynski|first3=Paul|last4=Li|first4=Shu-Ming|date=2014-12-10|title=Biosynthetic Pathways of Ergot Alkaloids|journal=Toxins|language=en|volume=6|issue=12|pages=3281–3295|doi=10.3390/toxins6123281|issn=2072-6651|pmc=4280535|pmid=25513893}}</ref> Reports of the toxic effects due to ergoline alkaloids date back to the 12th century.<ref name=":12">{{Cite journal|last=N.J.A. de Groot|first=Akosua|last2=van Dongen|first2=Pieter W.J.|last3=Vree|first3=Tom B.|last4=Hekster|first4=Yechiel A.|last5=van Roosmalen|first5=Jos|date=1998|title=Ergot Alkaloids|journal=Drugs|volume=56|issue=4|pages=523–535|doi=10.2165/00003495-199856040-00002|pmid=9806101|issn=0012-6667}}</ref> 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.<ref name=":02"/><ref name=":12"/> 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".<ref name=":02" />
Ergoline [[alkaloid]]s were first isolated from [[ergot]], a fungus that infects rye and causes [[ergotism]] or St. Anthony's fire.<ref>{{cite journal | vauthors = Gerhards N, Neubauer L, Tudzynski P, Li SM | title = Biosynthetic pathways of ergot alkaloids | journal = Toxins | volume = 6 | issue = 12 | pages = 3281–3295 | date = December 2014 | pmid = 25513893 | pmc = 4280535 | doi = 10.3390/toxins6123281 | doi-access = free }}</ref> Reports of the toxic effects due to ergoline alkaloids date back to the 12th century.<ref name=":12">{{cite journal | vauthors = de Groot AN, van Dongen PW, Vree TB, Hekster YA, van Roosmalen J | title = Ergot alkaloids. Current status and review of clinical pharmacology and therapeutic use compared with other oxytocics in obstetrics and gynaecology | journal = Drugs | volume = 56 | issue = 4 | pages = 523–535 | date = October 1998 | pmid = 9806101 | doi = 10.2165/00003495-199856040-00002 | s2cid = 46971443 }}</ref> 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.<ref name=":02"/><ref name=":12"/> 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".<ref name=":02" />


Attempts to characterize the activity of ergoline alkaloids began in 1907, with the isolation of ergotoxine by G. Barger and F. H. Carrin.<ref name=":2">{{Cite book|last=Sfetcu|first=Nicolae|title=Health & Drugs - Disease, Prescription & Medication|publisher=Lulu.com|year=2014|isbn=9781312039995}}</ref> 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 [[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.<ref name=":02" /><ref name=":2" /> The company, now renamed [[Novartis]], still retains its leadership in the product of ergot alkaloids though. In 1943, Arthur Stoll and [[Albert Hofmann]] reported the first total synthesis of an ergot alkaloid, ergometrine.<ref>{{Citation|last=Stoll|first=A.|title=Chapter 21 The Ergot Alkaloids|date=1965|work=The Alkaloids: Chemistry and Physiology|volume=8|pages=725–783|publisher=Elsevier|language=en|doi=10.1016/s1876-0813(08)60060-3|isbn=978-0-12-469508-5|last2=Hofmann|first2=A.}}</ref> Though the synthesis found no industrial application, this was a huge leap forward in the industry.
Attempts to characterize the activity of ergoline alkaloids began in 1907, with the isolation of ergotoxine by G. Barger and F. H. Carrin.<ref name=":2">{{Cite book| vauthors = Sfetcu N |title=Health & Drugs - Disease, Prescription & Medication|publisher=Lulu.com|year=2014|isbn=9781312039995}}</ref> 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.<ref name=":02" /><ref name=":2" /> 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.<ref>{{cite book | vauthors = Stoll A, Hofmann A | chapter = Chapter 21 The Ergot Alkaloids|date=1965| title = The Alkaloids: Chemistry and Physiology |volume=8 |pages=725–783 |publisher=Elsevier |language=en |doi=10.1016/s1876-0813(08)60060-3 |isbn=978-0-12-469508-5 }}</ref> Though the synthesis found no industrial application, this was a huge leap forward in the industry.


==Uses==
==Uses==
There are a variety of clinically useful ergoline derivatives for the purpose of [[vasoconstriction]], the treatment of [[migraine]]s, 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.<ref>{{Cite book|last=European Commission. Joint Research Centre.|title=Report on the 2017 proficiency test of the European Union reference laboratory for mycotoxins determination of ergot alkaloids in rye.|oclc=1060942360}}</ref> Following Arthur Stoll's isolation of ergometrine, the therapeutic use of ergoline derivatives became well explored.
There are a variety of clinically useful ergoline derivatives for the purpose of [[vasoconstriction]], the treatment of [[migraine]]s, 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.<ref>{{Cite book|last=European Commission. Joint Research Centre.|title=Report on the 2017 proficiency test of the European Union reference laboratory for mycotoxins determination of ergot alkaloids in rye.|oclc=1060942360}}</ref> 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.<ref name=":12"/> While used to facilitate child birth, ergoline derivatives can pass into [[breast milk]] and should not be used during breastfeeding.<ref name="kidsgrowth2">[http://www.kidsgrowth.org/resources/articledetail.cfm?id=471 kidsgrowth.org --> Drugs and Other Substances in Breast Milk] {{webarchive|url=https://archive.is/20070623011707/http://www.kidsgrowth.org/resources/articledetail.cfm?id=471|date=2007-06-23}} Retrieved on June 19, 2009.</ref> They are uterine contractors that can increase the risk of miscarriage during pregnancy.<ref name="Schardl20063"/>
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.<ref name=":12"/> While used to facilitate child birth, ergoline derivatives can pass into [[breast milk]] and should not be used during breastfeeding.<ref name="kidsgrowth2">[http://www.kidsgrowth.org/resources/articledetail.cfm?id=471 kidsgrowth.org --> Drugs and Other Substances in Breast Milk] {{webarchive|url=https://archive.today/20070623011707/http://www.kidsgrowth.org/resources/articledetail.cfm?id=471|date=2007-06-23}} Retrieved on June 19, 2009.</ref> They are uterine contractors that can increase the risk of miscarriage during pregnancy.<ref name="Schardl20063"/>


Another example of medically relevant ergoline alkaloids is [[ergotamine]], an alkaloid also found in ergot. It acts as a [[Vasoconstriction|vasoconstrictor]] and has been reported to control [[migraine]]s. From ergotamine, the [[anti-migraine]] drugs [[dihydroergotamine]] and [[methysergide]] were developed by Albert Hofmann.<ref>{{Cite book|last=Winkelman, Michael. Roberts, Thomas B.|title=Psychedelic medicine : new evidence for hallucinogenic substances as treatments|date=2007|publisher=Praeger Publishers|isbn=978-0-275-99023-7|oclc=85813998}}</ref>
Another example of medically relevant ergoline alkaloids is [[ergotamine]], an alkaloid also found in ergot. It acts as a [[Vasoconstriction|vasoconstrictor]] and has been reported to control [[migraine]]s. From ergotamine, the [[anti-migraine]] drugs [[dihydroergotamine]] and [[methysergide]] were developed by Albert Hofmann.<ref>{{Cite book| vauthors = Winkelman M, Roberts TB |title=Psychedelic medicine : new evidence for hallucinogenic substances as treatments|date=2007|publisher=Praeger Publishers|isbn=978-0-275-99023-7|oclc=85813998}}</ref>


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.<ref name=":3">{{Cite journal|last=Lataste|first=X.|date=February 1984|title=The History and Pharmacology of Dopamine Agonists|url=https://www.cambridge.org/core/product/identifier/S0317167100046266/type/journal_article|journal=Canadian Journal of Neurological Sciences |language=en|volume=11|issue=S1|pages=118–123|doi=10.1017/S0317167100046266|pmid=6713309|issn=0317-1671|doi-access=free}}</ref> 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.<ref name=":3" />
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.<ref name=":3">{{cite journal | vauthors = Lataste X | title = The history and pharmacology of dopamine agonists | journal = The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques | volume = 11 | issue = 1 Suppl | pages = 118–123 | date = February 1984 | pmid = 6713309 | doi = 10.1017/S0317167100046266 | doi-access = free }}</ref> 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.<ref name=":3" />


An infamous ergoline derivative is the [[psychedelic drug]] [[LSD]], a completely 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]].<ref name="http://www.incb.org/pdf/e/list/red.pdf2">http://www.incb.org/pdf/e/list/red.pdf {{webarchive|url=https://web.archive.org/web/20080227224025/http://www.incb.org/pdf/e/list/red.pdf|date=2008-02-27}}.</ref>
A famous ergoline derivative is the [[psychedelic drug]] [[LSD]], a [[Semisynthesis|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]].<ref name="http://www.incb.org/pdf/e/list/red.pdf2">{{cite web | title = List of Precursors and Chemicals Frequently Used in the Illicit Manufacture of Narcotic Drugs and Psychotropic Substances Under International Control | edition = Eleventh | date = January 2007 | work = International Narcotics Control Board | location = Vienna, Austria | url = http://www.incb.org/pdf/e/list/red.pdf | archive-url = https://web.archive.org/web/20080227224025/http://www.incb.org/pdf/e/list/red.pdf | archive-date=2008-02-27}}.</ref>


== Mechanism of action ==
== 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]].<ref name=":4">{{Cite journal|last=Mantegani|first=Sergio|last2=Brambilla|first2=Enzo|last3=Varasi|first3=Mario|date=May 1999|title=Ergoline derivatives: receptor affinity and selectivity|journal=Il Farmaco|volume=54|issue=5|pages=288–296|doi=10.1016/s0014-827x(99)00028-2|pmid=10418123|issn=0014-827X}}</ref> Ergoline alkaloids often interfere with multiple receptor sites, leading to negative side effects and adding to the challenge of drug development.
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]], [[Serotonin|serotonergic]], and [[antiserotonergic]].<ref name=":4">{{cite journal | vauthors = Mantegani S, Brambilla E, Varasi M | title = Ergoline derivatives: receptor affinity and selectivity | journal = Farmaco | volume = 54 | issue = 5 | pages = 288–296 | date = May 1999 | pmid = 10418123 | doi = 10.1016/s0014-827x(99)00028-2 }}</ref> Ergoline alkaloids often interfere with multiple receptor sites, leading to negative side effects and adding to the challenge of drug development.


=== Dopaminergic/antidopaminergic ===
=== Dopaminergic/antidopaminergic ===
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=== Serotonergic/antiserotonergic ===
=== Serotonergic/antiserotonergic ===
The primary challenges of developing serotnergic/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-HT<sub>1A</sub> agonist/5-HT<sub>2A</sub> antagonist, and [[mesulergine]], a 5-HT<sub>2A/2C</sub> antagonist.<ref name=":4" /> 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.<ref name=":4" /> This methodology has been used to develop selective 5-HT<sub>1A</sub> and 5-HT<sub>2A</sub> ergolines in particular.
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-HT<sub>1A</sub> agonist/5-HT<sub>2A</sub> antagonist, and [[mesulergine]], a 5-HT<sub>2A/2C</sub> antagonist.<ref name=":4" /> 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.<ref name=":4" /> This methodology has been used to develop selective 5-HT<sub>1A</sub> and 5-HT<sub>2A</sub> ergolines in particular.


==Ergoline derivatives==
==Ergoline derivatives==
There are 3 main classes of ergoline derivatives, the water-soluble [[amide]]s of ''[[lysergic acid]]'', the water-insoluble ''ergopeptines'' (i.e., ''ergo[[peptides]]''), and the ''clavine'' group.<ref name="Schardl2006">{{cite journal|vauthors=Schardl CL, Panaccione DG, Tudzynski P |year=2006|title=Ergot alkaloids&nbsp;– biology and molecular biology|volume=63|pages=45–86|pmid=17133714|doi=10.1016/S1099-4831(06)63002-2|series=The Alkaloids: Chemistry and Biology|isbn=978-0-12-469563-4}}</ref>
There are 3 main classes of ergoline derivatives, the water-soluble [[amide]]s of ''[[lysergic acid]]'', the water-insoluble ''ergopeptines'' (i.e., ''ergo[[peptides]]''), and the ''clavine'' group.<ref name="Schardl2006">{{cite book|vauthors=Schardl CL, Panaccione DG, Tudzynski P |year=2006|title=Ergot alkaloids&nbsp;– biology and molecular biology|volume=63|pages=45–86|pmid=17133714|doi=10.1016/S1099-4831(06)63002-2|series=The Alkaloids: Chemistry and Biology|isbn=978-0-12-469563-4}}</ref>


===Lysergic acid amides===
===Lysergic acid amides===
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===Peptide alkaloids===<!-- Ergotoxine, Ergopeptine and other titles redirect here -->
===Peptide alkaloids===<!-- Ergotoxine, Ergopeptine and other titles redirect here -->
Peptide ergot alkaloids or '''[[ergopeptines]]''' (also known as ''ergopeptides'') are ergoline derivatives that contain a tri[[peptide]] 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.<ref>{{cite journal|last=G. Floss|first=Heinz|title=Biosynthesis of Ergot Alkaloids and Related Compounds|journal=Tetrahedron Report|year=1976|volume=32|issue=14|pages=873–912|doi=10.1016/0040-4020(76)85047-8}}</ref> Some of the important ergopeptines are summarized below.<ref>{{Cite journal|last1=Yates |first1=S. G. |last2=Plattner |first2=R. D. |last3=Garner |first3=G. B. |doi=10.1021/jf00064a038 |title=Detection of ergopeptine alkaloids in endophyte-infected, toxic Ky-31 tall fescue by mass spectrometry/mass spectrometry |journal=Journal of Agricultural and Food Chemistry |volume=33 |issue=4 |pages=719 |year=1985 |url=http://ddr.nal.usda.gov/bitstream/10113/23986/1/IND86034816.pdf }}{{dead link|date=December 2016 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> 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.
Peptide ergot alkaloids or '''[[ergopeptines]]''' (also known as ''ergopeptides'') are ergoline derivatives that contain a tri[[peptide]] 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.<ref>{{cite journal| vauthors = Floss HG |title=Biosynthesis of Ergot Alkaloids and Related Compounds|journal=Tetrahedron Report|date= January 1976 |volume=32|issue=14|pages=873–912|doi=10.1016/0040-4020(76)85047-8}}</ref> Some of the important ergopeptines are summarized below.<ref>{{Cite journal| vauthors = Yates SG, Plattner RD, Garner GB |doi=10.1021/jf00064a038 |title=Detection of ergopeptine alkaloids in endophyte-infected, toxic Ky-31 tall fescue by mass spectrometry/mass spectrometry |journal=Journal of Agricultural and Food Chemistry |volume=33 |issue=4 |pages=719–722 |date = July 1985 |url=http://ddr.nal.usda.gov/bitstream/10113/23986/1/IND86034816.pdf }}{{dead link|date=December 2016 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> 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 ''[[Ergocryptine|alpha]]''- and [[Beta-Ergocryptine|''beta''-ergocryptine]].


* Ergotoxine group ([[valine]] as the amino acid attached to the ergoline moiety, at R<sup>2</sup> below)
* Ergotoxine group ([[valine]] as the amino acid attached to the ergoline moiety, at R<sup>2</sup> below)
Line 170: Line 171:
{| class="wikitable" style="float:right"
{| class="wikitable" style="float:right"
|-
|-
! Name !! R<sup>1</sup> !! R<sup>2</sup> !! R<sup>3</sup> !! Amino acid at R<sup>3</sup>
! Name !! R<sup>1</sup> !! R<sup>2</sup> !! R<sup>3</sup> !! Amino acid at R<sup>2</sup> !! Amino acid at R<sup>3</sup>
|-
|-
| [[Ergocristine]] || || [[Isopropyl|CH(CH<sub>3</sub>)<sub>2</sub>]] || [[benzyl]] || [[Phenylalanine]]
| [[Ergocristine]] || || [[Isopropyl|CH(CH<sub>3</sub>)<sub>2</sub>]] || [[benzyl]] || Valine || [[Phenylalanine]]
|-
|-
| [[Ergocornine]] || || CH(CH<sub>3</sub>)<sub>2</sub> || CH(CH<sub>3</sub>)<sub>2</sub> || [[Valine]]
| [[Ergocornine]] || || CH(CH<sub>3</sub>)<sub>2</sub> || CH(CH<sub>3</sub>)<sub>2</sub> || Valine || [[Valine]]
|-
|-
| ''alpha''-[[Ergocryptine]] || || CH(CH<sub>3</sub>)<sub>2</sub> || CH<sub>2</sub>CH(CH<sub>3</sub>)<sub>2</sub> || [[Leucine]]
| ''alpha''-[[Ergocryptine]] || || CH(CH<sub>3</sub>)<sub>2</sub> || CH<sub>2</sub>CH(CH<sub>3</sub>)<sub>2</sub> || Valine || [[Leucine]]
|-
|-
| [[beta-Ergocryptine|''beta''-Ergocryptine]] || || CH(CH<sub>3</sub>)<sub>2</sub> || CH(CH<sub>3</sub>)CH<sub>2</sub>CH<sub>3</sub> (''S'') || [[Isoleucine]]
| [[beta-Ergocryptine|''beta''-Ergocryptine]] || || CH(CH<sub>3</sub>)<sub>2</sub> || CH(CH<sub>3</sub>)CH<sub>2</sub>CH<sub>3</sub> (''S'') || Valine || [[Isoleucine]]
|-
|-
| [[Ergotamine]] || || [[Methyl|CH<sub>3</sub>]] || benzyl || Phenylalanine
| [[Ergotamine]] || || [[Methyl|CH<sub>3</sub>]] || benzyl || [[Alanine]] || Phenylalanine
|-
|-
| [[Ergovaline]] || || CH<sub>3</sub> || CH(CH<sub>3</sub>)<sub>2</sub> || Valine
| [[Ergovaline]] || || CH<sub>3</sub> || CH(CH<sub>3</sub>)<sub>2</sub> || Alanine || Valine
|-
|-
| ''alpha''-[[Ergosine]] || || CH<sub>3</sub> || CH<sub>2</sub>CH(CH<sub>3</sub>)<sub>2</sub> || Leucine
| ''alpha''-[[Ergosine]] || || CH<sub>3</sub> || CH<sub>2</sub>CH(CH<sub>3</sub>)<sub>2</sub> || Alanine || Leucine
|-
|-
| [[beta-Ergosine|''beta''-Ergosine]] || || CH<sub>3</sub> || CH(CH<sub>3</sub>)CH<sub>2</sub>CH<sub>3</sub> (''S'') || Isoleucine
| [[beta-Ergosine|''beta''-Ergosine]] || || CH<sub>3</sub> || CH(CH<sub>3</sub>)CH<sub>2</sub>CH<sub>3</sub> (''S'') || Alanine || Isoleucine
|-
|-
| [[Bromocriptine]] ([[semisynthetic]]) || [[Bromine|Br]] || CH(CH<sub>3</sub>)<sub>2</sub> || CH<sub>2</sub>CH(CH<sub>3</sub>)<sub>2</sub> || Leucine
| [[Bromocriptine]] ([[semisynthetic]]) || [[Bromine|Br]] || CH(CH<sub>3</sub>)<sub>2</sub> || CH<sub>2</sub>CH(CH<sub>3</sub>)<sub>2</sub> || Valine || Leucine
|}
|}


Line 209: Line 210:
** CAS number: {{CAS|18016-80-3}}
** CAS number: {{CAS|18016-80-3}}


==See also==
== See also ==
* [[Ergotism]]
* [[Ergotism]]
* [[Ergot]]
* [[Ergot]]
Line 217: Line 218:
* [[Albert Hofmann]]
* [[Albert Hofmann]]


==References==
== References ==
{{reflist}}
{{reflist}}


==External links==
== External links ==
* [https://web.archive.org/web/20040411102155/http://www.people.vcu.edu/~asneden/The%20Ergot%20Alkaloids.pdf The Ergot Alkaloids (A. T. Sneden)]
* [https://web.archive.org/web/20040411102155/http://www.people.vcu.edu/~asneden/The%20Ergot%20Alkaloids.pdf The Ergot Alkaloids (A. T. Sneden)]
* [https://web.archive.org/web/20040720041016/http://www.world-of-fungi.org/Mostly_Medical/Ziad_Madlom/Ergot_alkaloids.htm The Ergot Alkaloids Story (Z. Madlom)]
* [https://web.archive.org/web/20040720041016/http://www.world-of-fungi.org/Mostly_Medical/Ziad_Madlom/Ergot_alkaloids.htm The Ergot Alkaloids Story (Z. Madlom)]
Line 232: Line 233:
{{Ergolines}}
{{Ergolines}}


[[Category:Alkaloids]]
[[Category:Tryptamine alkaloids]]
[[Category:Quinoline alkaloids]]
[[Category:Ergolines| ]]
[[Category:Ergolines| ]]
[[Category:Alkaloids found in fungi]]
[[Category:Alkaloids found in fungi]]

Latest revision as of 09:21, 23 May 2023

Ergoline
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
FormulaC14H16N2
Molar mass212.296 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 checkY
  • Key:RHGUXDUPXYFCTE-ZWNOBZJWSA-N checkY
  (verify)

Ergoline is a chemical compound whose structural skeleton is contained in a variety of alkaloids, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being ergine, were initially characterized in ergot. Some of these are implicated in the condition ergotism, which can take a convulsive form 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.[1]

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.[2]

Natural occurrence

[edit]

Ergoline alkaloids are found in lower fungi and some species of flowering plants: the Mexican species Turbina corymbosa and Ipomoea tricolor of the Convolvulaceae (morning glory) family, the seeds of which were identified as the psychedelic plant drugs known as "ololiuhqui" and "tlitliltzin", respectively.[3][4] The principal alkaloids in the seeds are ergine and its optical isomer isoergine, with several other lysergic acid derivatives and clavines present in lesser amounts. The Hawaiian species Argyreia nervosa includes similar alkaloids. It is possible, though not proven, that ergine or isoergine are responsible for the psychedelic effects. There may be a fungal origin of the ergoline alkaloids also in the Convolvulaceae. Like the ergot alkaloids in some monocot plants, the ergoline alkaloids found in the plant Ipomoea asarifolia (Convolvulaceae) are produced by a seed-transmitted endophytic clavicipitaceous fungus.[5]

History

[edit]

Ergoline alkaloids were first isolated from ergot, a fungus that infects rye and causes ergotism or St. Anthony's fire.[6] Reports of the toxic effects due to ergoline alkaloids date back to the 12th century.[7] 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.[1][7] 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".[1]

Attempts to characterize the activity of ergoline alkaloids began in 1907, with the isolation of ergotoxine by G. Barger and F. H. Carrin.[8] 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.[1][8] 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.[9] Though the synthesis found no industrial application, this was a huge leap forward in the industry.

Uses

[edit]

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.[10] 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.[7] While used to facilitate child birth, ergoline derivatives can pass into breast milk and should not be used during breastfeeding.[11] They are uterine contractors that can increase the risk of miscarriage during pregnancy.[3]

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.[12]

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.[13] 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.[13]

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.[14]

Mechanism of action

[edit]

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.[15] Ergoline alkaloids often interfere with multiple receptor sites, leading to negative side effects and adding to the challenge of drug development.

Dopaminergic/antidopaminergic

[edit]

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.[15] 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.[15]

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.[15] The antagonist or agonist behavior of the ergolines are substrate dependent and mixed agonist/antagonist behaviors of ergoline derivatives have been reported.[15]

Serotonergic/antiserotonergic

[edit]

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.[15] 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.[15] This methodology has been used to develop selective 5-HT1A and 5-HT2A ergolines in particular.

Ergoline derivatives

[edit]

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.[16]

Lysergic acid amides

[edit]
Main article: Lysergamides
  • Ergine (LSA, D-lysergic acid amide, LAA, LA-111)
  • Ergonovine (ergobasine)
    • INN: ergometrine
    • IUPAC name: (8beta(S))-9,10-didehydro-N-(2-hydroxy-1-methylethyl)-6-methyl-ergoline-8-carboxamide
    • CAS number: 60-79-7
  • Methergine (ME-277)
    • INN: methylergometrine
    • IUPAC name: (8beta(S))-9,10-didehydro-N-(1-(hydroxymethyl)propyl)-6-methyl-ergoline-8-carboxamide
    • CAS number: 113-42-8
  • Methysergide (UML-491)
    • INN: methysergide
    • IUPAC name: (8beta)-9,10-didehydro-N-(1-(hydroxymethyl)propyl)-1,6-dimethyl-ergoline-8-carboxamide
    • CAS number: 361-37-5
  • LSD (D-lysergic acid diethylamide, LSD-25)
    • INN: lysergide
    • IUPAC name: (8beta)-9,10-didehydro-N,N-diethyl-6-methyl-ergoline-8-carboxamide
    • CAS number: 50-37-3
  • LSH (D-lysergic acid α-hydroxyethylamide)
    • IUPAC name: 9,10-didehydro-N-(1-hydroxyethyl)-6-methylergoline-8-carboxamide
    • CAS number: 3343-15-5

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

Substituted ergine (structural formula)
Substituted ergine (structural formula)
Name R1 R2 R3
Ergine H H H
Ergonovine H CH(CH3)CH2OH H
Methergine H CH(CH2CH3)CH2OH H
Methysergide CH3 CH(CH2CH3)CH2OH H
LSD H CH2CH3 CH2CH3

Peptide alkaloids

[edit]

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.[17] Some of the important ergopeptines are summarized below.[18] 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.

  • Ergotoxine group (valine as the amino acid attached to the ergoline moiety, at R2 below)
    • Ergocristine
    • Ergocornine
      • IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2',5'-bis(1-methylethyl)-, (5'-alpha)-
      • CAS number: 564-36-3
    • alpha-Ergocryptine
      • IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)-, (5'alpha)-
      • CAS number: 511-09-1
    • beta-Ergocryptine
      • IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-(1-methylethyl)-5'-(1-methylpropyl)-, (5'alpha(S))-
      • CAS number: 20315-46-2
  • Ergotamine group (alanine at R2)
    • Ergotamine
      • IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-methyl-5'-(phenylmethyl)-, (5'-alpha)-
      • CAS number: 113-15-5
    • Ergovaline
      • IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-methyl-5'-(1-methylethyl)-, (5'alpha)-
      • CAS number: 2873-38-3
    • alpha-Ergosine
      • IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-methyl-5'-(2-methylpropyl)-, (5'-alpha)-
      • CAS number: 561-94-4
    • beta-Ergosine
      • IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-methyl-5'-(1-methylpropyl)-, (5'-alpha(S))-
      • CAS number: 60192-59-8
Ergopeptides (structural formula)
Ergopeptides (structural formula)
Name R1 R2 R3 Amino acid at R2 Amino acid at R3
Ergocristine CH(CH3)2 benzyl Valine Phenylalanine
Ergocornine CH(CH3)2 CH(CH3)2 Valine Valine
alpha-Ergocryptine CH(CH3)2 CH2CH(CH3)2 Valine Leucine
beta-Ergocryptine CH(CH3)2 CH(CH3)CH2CH3 (S) Valine Isoleucine
Ergotamine CH3 benzyl Alanine Phenylalanine
Ergovaline CH3 CH(CH3)2 Alanine Valine
alpha-Ergosine CH3 CH2CH(CH3)2 Alanine Leucine
beta-Ergosine CH3 CH(CH3)CH2CH3 (S) Alanine Isoleucine
Bromocriptine (semisynthetic) Br CH(CH3)2 CH2CH(CH3)2 Valine Leucine

Clavines

[edit]

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

[edit]

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

See also

[edit]

References

[edit]
  1. ^ a b c d Schiff PL (October 2006). "Ergot and its alkaloids". American Journal of Pharmaceutical Education. 70 (5): 98. doi:10.5688/aj700598. PMC 1637017. PMID 17149427.
  2. ^ 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.
  3. ^ a b 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.
  4. ^ 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.
  5. ^ Steiner U, Ahimsa-Müller MA, Markert A, Kucht S, Gross J, Kauf N, et al. (August 2006). "Molecular characterization of a seed transmitted clavicipitaceous fungus occurring on dicotyledoneous plants (Convolvulaceae)". Planta. 224 (3): 533–544. doi:10.1007/s00425-006-0241-0. PMID 16525783. S2CID 25682792.
  6. ^ Gerhards N, Neubauer L, Tudzynski P, Li SM (December 2014). "Biosynthetic pathways of ergot alkaloids". Toxins. 6 (12): 3281–3295. doi:10.3390/toxins6123281. PMC 4280535. PMID 25513893.
  7. ^ a b c de Groot AN, van Dongen PW, Vree TB, Hekster YA, van Roosmalen J (October 1998). "Ergot alkaloids. Current status and review of clinical pharmacology and therapeutic use compared with other oxytocics in obstetrics and gynaecology". Drugs. 56 (4): 523–535. doi:10.2165/00003495-199856040-00002. PMID 9806101. S2CID 46971443.
  8. ^ a b Sfetcu N (2014). Health & Drugs - Disease, Prescription & Medication. Lulu.com. ISBN 9781312039995.
  9. ^ Stoll A, Hofmann A (1965). "Chapter 21 The Ergot Alkaloids". The Alkaloids: Chemistry and Physiology. Vol. 8. Elsevier. pp. 725–783. doi:10.1016/s1876-0813(08)60060-3. ISBN 978-0-12-469508-5.
  10. ^ 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.
  11. ^ kidsgrowth.org --> Drugs and Other Substances in Breast Milk Archived 2007-06-23 at archive.today Retrieved on June 19, 2009.
  12. ^ Winkelman M, Roberts TB (2007). Psychedelic medicine : new evidence for hallucinogenic substances as treatments. Praeger Publishers. ISBN 978-0-275-99023-7. OCLC 85813998.
  13. ^ a b Lataste X (February 1984). "The history and pharmacology of dopamine agonists". The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques. 11 (1 Suppl): 118–123. doi:10.1017/S0317167100046266. PMID 6713309.
  14. ^ "List of Precursors and Chemicals Frequently Used in the Illicit Manufacture of Narcotic Drugs and Psychotropic Substances Under International Control" (PDF). International Narcotics Control Board (Eleventh ed.). Vienna, Austria. January 2007. Archived from the original (PDF) on 2008-02-27..
  15. ^ a b c d e f g Mantegani S, Brambilla E, Varasi M (May 1999). "Ergoline derivatives: receptor affinity and selectivity". Farmaco. 54 (5): 288–296. doi:10.1016/s0014-827x(99)00028-2. PMID 10418123.
  16. ^ 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.
  17. ^ Floss HG (January 1976). "Biosynthesis of Ergot Alkaloids and Related Compounds". Tetrahedron Report. 32 (14): 873–912. doi:10.1016/0040-4020(76)85047-8.
  18. ^ 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]
[edit]
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