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Ergoline

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Ergoline
Identifiers
  • (6aR)- 4,6,6a,7,8,9,10,10a- octahydroindolo [4,3-fg] quinoline
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H16N2
Molar mass212.29g/mol g·mol−1

Ergoline is a chemical compound whose structural skeleton is contained in a diverse range of alkaloids including a few psychedelic drugs (ololiuhqui, LSD). Ergoline derivatives are used clinically for the purpose of vasoconstriction (5-HT1 receptor agonists—ergotamine) and in the treatment of migraine (used with caffeine) and Parkinson's disease, some are implicated in the disease ergotism, causing convulsive and gangrenous symptoms.

Uses

In addition to the naturally occurring ergonovine (used as an oxytocic) and ergotamine (a vasoconstrictor used to control migraine), synthetic derivatives of importance are the oxytocic methergine, the anti-migraine drugs dihydroergotamine and methysergide, hydergine (a mixture of dihydroergotoxine mesylates, 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 drug LSD. Ergometrine and ergotamine are included as table I precursors in the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.[1]

They pass into breast milk and should be avoided during breastfeeding.[2]

Chemistry

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.[3]

Lysergic acid amides

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

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

These compounds have a tripeptide 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.

Ergopeptides (structural formula)
Ergopeptides (structural formula)
Name R1 R2 R3
Ergotamine CH3 benzyl
Ergocristine CH(CH3)2 benzyl
Ergocornine CH(CH3)2 CH(CH3)2
Ergocryptine CH(CH3)2 CH2CH(CH3)2
Bromocriptine Br CH(CH3)2 CH2CH(CH3)2
Ergovaline CH3 CH(CH3)2


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:

Natural occurrence

Ergoline alkaloids is found in lower fungi and two species of flowering plants: the 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"[verification needed][citation needed]. 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 hallucinogenic 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 epiphytic clavicipitaceous fungus.[4]

History

Ergoline alkaloids 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 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 toxicity 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 synthetic derivatives began.

In 1960, Albert Hofmann (discoverer of methergine, dihydroergotamine, Hydergine and lysergic acid diethylamide) delivered a speech that was to cause shockwaves of incredulity and disbelief in the scientific community.

Hofmann's result was later confirmed by other studies. Hofmann's discovery is an important landmark in the research of ergot alkaloids

See also

References

  1. ^ http://www.incb.org/pdf/e/list/red.pdf
  2. ^ kidsgrowth.org --> Drugs and Other Substances in Breast Milk Retrieved on June 19, 2009
  3. ^ Schardl CL, Panaccione DG, Tudzynski P (2006). "Ergot alkaloids – biology and molecular biology". The Alkaloids: Chemistry and Biology. 63: 45–86. doi:10.1016/S1099-4831(06)63002-2. PMID 17133714.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Steiner U. et al. (2006) Molecular characterization of a seed transmitted clavicipitaceous fungus occurring on dicotyledoneous plants (Convolvulaceae). Planta 224: 533-544. PMID 16525783
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