Ergoline
621512
226024096
2008-07-16T14:14:48Z
Cacycle
83784
rv overlinking (per styleguide) and sortable (way too small for sortable)
{{drugbox |
| IUPAC_name = (6a''R'')-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-''fg'']quinoline
| image = Ergoline.png
| CAS_number = 478-88-6
| ATC_prefix =
| ATC_suffix =
| PubChem = 3083577
| DrugBank =
| C=14|H=16|N=2
| molecular_weight = 212.29g/mol
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category=
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status =
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}}
'''Ergoline''' is a [[chemical]] [[Chemical compound|compound]] whose structural skeleton is contained in a diverse range of [[alkaloids]] and a few [[psychedelic]] [[Psychoactive drug|drugs]] ([[ololiuhqui]], [[LSD]]). Ergoline derivatives are used clinically for the purpose of [[vasoconstriction]] ([[5-HT1 receptor|5-HT<sub>1</sub>]] receptor agonists - ergotamine) and in the treatment of [[migraine]] (used with [[caffeine]]) and [[Parkinson's disease]], some are implicated in the disease [[ergotism]]. Ergometrine and ergotamine are listed as Table I precursors under the [[United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances]].<ref name="http://www.incb.org/pdf/e/list/red.pdf">[http://www.incb.org/pdf/e/list/red.pdf http://www.incb.org/pdf/e/list/red.pdf]</ref> </sup>
==Chemistry==
{{splitsection|Ergoline derivatives}}
There are three 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|author=Schardl CL, Panaccione DG, Tudzynski P|year=2006|title=Ergot alkaloids – biology and molecular biology|journal=The Alkaloids: Chemistry and Biology|volume=63|pages=45–86|pmid=17133714|doi=10.1016/S1099-4831(06)63002-2}}</ref>
===Lysergic acid amides===
{{main|Lysergamides}}
* [[Ergine]] (LSA, <small>D</small>-lysergic acid amide, LAA, LA-111)
** [[IUPAC name]]: 9,10-didehydro-6-methylergoline-8beta-carboxamide
** [[CAS number]]: 478-94-4
* [[Ergonovine]] (ergobasine)
** [[International Nonproprietary Name|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)
** [[International Nonproprietary Name|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)
** [[International Nonproprietary Name|INN]]: methysergide
** [[IUPAC name]]: (8''beta'')−9,10-didehydro-''N''-(1-(hydroxymethyl)propyl)−1,6-dimethyl-ergoline-8-carboxamide
** [[CAS number]]: 361-37-5
* [[LSD]] (<small>D</small>-lysergic acid diethylamide, LSD-25)
** [[International Nonproprietary Name|INN]]: lysergide
** [[IUPAC name]]: (8beta)−9,10-didehydro-N,N-diethyl-6-methyl-ergoline-8-carboxamide
** [[CAS number]]: 50-37-3
The relationship between these compounds is summarized in the following [[structural formula]] and table of substitutions.
[[Image:Ergines.png|left|Substituted ergine (structural formula)]]
{| border=1 align=left
!Name !! R1 !! N1 !! N2
|-
| [[Ergine]] || H || H || H
|-
| [[Ergonovine]] || H || CH(CH<sub>3</sub>)CH<sub>2</sub>OH || H
|-
| [[Methergine]] || H || CH(CH<sub>2</sub>CH<sub>3</sub>)CH<sub>2</sub>OH || H
|-
| [[Methysergide]] || [[methyl|CH<sub>3</sub>]] || CH(CH<sub>2</sub>CH<sub>3</sub>)CH<sub>2</sub>OH || H
|-
| [[LSD]] || H || [[Ethyl|CH<sub>2</sub>CH<sub>3</sub>]] || [[Ethyl|CH<sub>2</sub>CH<sub>3</sub>]]
|}
<br style="clear:both;">
===Peptide alkaloids===
These compounds have a tri[[peptide]] structure attached to the basic ergoline ring, in the same location as the [[amide]] group of the lysergic acid derivatives. This tripeptide moiety contains an unusual [[cyclol]] bond >N-C(OH)< at the juncture between the two [[lactam]] rings. Some of the important '''ergopeptines''' (also known as ''ergopeptides'') are summarized below. 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.
* [[Ergotamine]]
** [[IUPAC name]]: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-methyl-5'-(phenylmethyl)-, (5'-alpha)- (9CI)
** [[CAS number]]: 113-15-5
* [[Ergocristine]]
** [[IUPAC name]]: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-(1-methylethyl)−5'-(phenylmethyl)-, (5'-alpha)-
** [[CAS number]]: 511-08-0
* [[Ergocornine]]
** [[IUPAC name]]: Ergotaman-3',6',18-trione, 12'-hydroxy-2',5'-bis(1-methylethyl)-, (5'-alpha)-
** [[CAS number]]: 564-36-3
* [[Ergocryptine]]
** [[IUPAC name]]:Ergotaman-3',6',18-trione, 12'-hydroxy-2'-(1-methylethyl)−5'-(2-methylpropyl)-, (5'alpha)- (9CI)
** [[CAS number]]: 511-09-1
* [[Bromocriptine]] ([[International Nonproprietary Name|INN]])
** [[IUPAC name]]: Ergotaman-3',6',18-trione, 2-bromo-12'-hydroxy-2'-(1-methylethyl)−5'-(2-methylpropyl)-, (5'alpha)-
** [[CAS number]]: 25614-03-3
* [[Ergovaline]]
** [[IUPAC name]]: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-methyl-5'-(1-methylethyl)-, (5'alpha)-
** [[CAS number]]: 2873-38-3
[[Image:Ergopeptides.png|left|Ergopeptides (structural formula)]]
{| class="wikitable" style="float:right"
|-
! Name !! R2 !! R2' !! R5'
|-
| [[Ergotamine]] || || [[Methyl|CH<sub>3</sub>]] || [[benzyl]]
|-
| [[Ergocristine]] || || CH(CH<sub>3</sub>)<sub>2</sub> || [[benzyl]]
|-
| [[Ergocornine]] || || CH(CH<sub>3</sub>)<sub>2</sub> || CH(CH<sub>3</sub>)<sub>2</sub>
|-
| [[Ergocryptine]] || || CH(CH<sub>3</sub>)<sub>2</sub> || CH<sub>2</sub>CH(CH<sub>3</sub>)<sub>2</sub>
|-
| [[Bromocriptine]] || [[Bromine|Br]] || CH(CH<sub>3</sub>)<sub>2</sub> || CH<sub>2</sub>CH(CH<sub>3</sub>)<sub>2</sub>
|-
| [[Ergovaline]] || || [[Methyl|CH<sub>3</sub>]] || CH(CH<sub>3</sub>)<sub>2</sub>
|}
<br style="clear:both">
===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'''.
===Others===
Some synthetic ergoline derivatives do not fall easily into any of the above groups. Some examples are:
* [[Pergolide]] ([[International Nonproprietary Name|INN]])
** [[IUPAC name]]: (8beta)−8-((methylthio)methyl)−6-propyl-ergoline
** [[CAS number]]: 66104-22-1
* [[Lisuride]] ([[International Nonproprietary Name|INN]])
** [[IUPAC name]]: 3-(9,10-didehydro-6-methylergolin-8alpha-yl)−1,1-diethylurea
** [[CAS number]]: 18016-80-3
==History & Uses==
Ergoline [[alkaloid]]s were first isolated from [[ergot]], a fungus that infects grain and causes the disease [[ergotism]]. Ergot also has a long history of medicinal use, which led to attempts to characterize its activity [[chemistry|chemically]]. This began in [[1907]] with the isolation by G. Barger and F. H. Carrin of ergotoxine, so-named since it appeared to exhibit more of the [[toxic]]ity of ergot than its therapeutic qualities. With the isolation of '''ergotamine''' in [[1918]] by A. Stoll came the first therapeutic use of isolated ergoline alkaloids.
With the determination of the basic [[chemical structure]] of the ergot alkaloids in the early 1930s, an era of intensive exploration of [[Chemical synthesis|synthetic]] derivatives began. In addition to the naturally occurring '''ergonovine''' (used as an [[oxytocic]]) and '''ergotamine''' (an [[analgesic]] used to control [[migraine]]), synthetic derivatives of continuing importance today are the oxytocic '''methergine''', the anti-migraine drugs [[dihydroergotamine]] and [[methysergide]], '''Hydergine''' (a mixture of dihydroergotoxine mesylates, [[International Nonproprietary Name|INN]]: ergoline mesylates), and [[bromocriptine]], used for numerous purposes including treatment of [[Parkinson's disease]]. Newer synthetic ergolines used for Parkinson's disease include [[pergolide]] and [[lisuride]]. Perhaps the most famous ergoline derivative of all is the [[psychedelic]] [[Psychoactive drug|drug]] [[LSD]].
In [[1960]], [[Albert Hofmann]] (discoverer of methergine, dihydroergotamine, Hydergine and LSD) delivered a speech that was to cause shockwaves of incredulity and disbelief in the scientific community. Ergoline alkaloids, previously only known from the lower [[fungi]], had been found in two species of [[flowering plant]]s. These were the [[mexico|Mexican]] species ''[[Rivea corymbosa]]'' and ''[[Ipomoea violacea]]'' of the [[Convolvulaceae]] (morning glory) family, the seeds of which were identified as the psychedelic plant drugs known as "[[ololiuhqui]]" and "[[tlitliltzin]]"{{Verify source|date=November 2007}}{{Fact|date=November 2007}}<!-- usually this is from Ipomoea tricolor -->. Hofmann's result was later confirmed by other studies. 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]]'' was later found to include similar alkaloids. It is possible, though not proven, that [[ergine]] or isoergine are responsible for the [[Psychedelics, dissociatives and deliriants|hallucinogen]]ic effects. However, while Hofmann's discovery is an important landmark in the research of ergot alkaloids, a recent study has provided evidence for 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 [[epiphyte|epiphytic]] clavicipitaceous [[fungus]].<ref name="">Steiner U. et al. (2006) Molecular characterization of a seed transmitted clavicipitaceous fungus occurring on dicotyledoneous plants (Convolvulaceae). Planta 224: 533-544. PMID 16525783</ref>
==See also==
* [[Ergotism]]
* [[Ergot]]
* [[LSD]]
* [[Ergine]]
* [[Migraine]]
* [[Albert Hofmann]]
==References==
{{reflist}}
==External links==
* [http://www.people.vcu.edu/~asneden/The%20Ergot%20Alkaloids.pdf The Ergot Alkaloids (A. T. Sneden)]
* [http://www.world-of-fungi.org/Mostly_Medical/Ziad_Madlom/Ergot_alkaloids.htm The Ergot Alkaloids Story (Z. Madlom)]
* [http://www.tacethno.com/info/claviceps/ergotalkfungi.txt The Psychoactive Ergot Alkaloids and their occurrence in the Microfungi — M. P. Bock and D. G. Parbery]
* [http://www.erowid.org/plants/mushrooms/references/other/1971_hofmann_bulletin-narcotics.shtml Hofmann, A. ''Teonanácatl and Ololiuqui, two ancient magic drugs of Mexico'' Bulletin on Narcotics 1971 1 3]
* [http://www.erowid.org/library/books_online/tihkal/tihkal26.shtml TiHKAL (A & A Shulgin) #26]
{{Ergolines}}
[[Category:Biomolecules]]
[[Category:Drugs]]
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