Ergoline is a chemical compound whose structural skeleton is contained in a variety of
alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...
s, referred to as ergoline derivatives or ergoline alkaloids. Ergoline alkaloids, one being
ergine
Ergine, also known as d-lysergic acid amide (LSA) and d-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, Hawai ...
, were initially characterized in
ergot
Ergot ( ) or ergot fungi refers to a group of fungi of the genus ''Claviceps''.
The most prominent member of this group is ''Claviceps purpurea'' ("rye ergot fungus"). This fungus grows on rye and related plants, and produces alkaloids that ca ...
. 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
Lysergic acid, also known as -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'' ...
, used primarily in the manufacture of semi-synthetic derivatives.
Others, such as
lysergic acid diethylamide
Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
, better known as LSD, a
semi-synthetic
Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...
derivative, and
ergine
Ergine, also known as d-lysergic acid amide (LSA) and d-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, Hawai ...
, a natural derivative found in ''
Argyreia nervosa
''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 me ...
'', ''
Ipomoea tricolor
''Ipomoea tricolor'', the Mexican morning glory or just morning glory, is a species of flowering plant in the family Convolvulaceae, native to the New World tropics, and widely cultivated and naturalised elsewhere. It is an herbaceous annual or ...
'' and related species, are known
psychedelic
Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science of ...
substances.
Natural occurrence
Ergoline alkaloids are found in lower
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
and some species of
flowering plant
Flowering plants are plants that bear flowers and fruits, and form the clade Angiospermae (), commonly called angiosperms. The term "angiosperm" is derived from the Greek words ('container, vessel') and ('seed'), and refers to those plants th ...
s: the
Mexican species ''
Turbina corymbosa
''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.
Description and names ...
'' and ''
Ipomoea tricolor
''Ipomoea tricolor'', the Mexican morning glory or just morning glory, is a species of flowering plant in the family Convolvulaceae, native to the New World tropics, and widely cultivated and naturalised elsewhere. It is an herbaceous annual or ...
'' of the
Convolvulaceae
Convolvulaceae (), commonly called the bindweeds or morning glories, is a family of about 60 genera and more than 1,650 species. These species are primarily herbaceous vines, but also include trees, shrubs and herbs. The tubers of several spec ...
(morning glory) family, the seeds of which were identified as the psychedelic plant drugs known as "ololiuhqui" and "tlitliltzin", respectively.
The principal alkaloids in the seeds are ergine and its
optical isomer
In chemistry, a molecule or ion is called chiral () if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes. This geometric property is called chirality (). The terms are d ...
isoergine, with several other lysergic acid derivatives and clavines present in lesser amounts. The
Hawaii
Hawaii ( ; haw, Hawaii or ) is a state in the Western United States, located in the Pacific Ocean about from the U.S. mainland. It is the only U.S. state outside North America, the only state that is an archipelago, and the only stat ...
an species ''
Argyreia nervosa
''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 me ...
'' includes similar alkaloids. It is possible, though not proven, that
ergine
Ergine, also known as d-lysergic acid amide (LSA) and d-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, Hawai ...
or isoergine are responsible for the
psychedelic
Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science of ...
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
''Ipomoea asarifolia'', the ginger-leaf morning-glory, is a species of plant in the family Convolvulaceae, of the genus ''Ipomoea
''Ipomoea'' () is the largest genus in the plant family Convolvulaceae, with over 600 species. It is a larg ...
'' (Convolvulaceae) are produced by a seed-transmitted
endophytic
An endophyte is an endosymbiont, often a bacterium or fungus, that lives within a plant for at least part of its life cycle without causing apparent disease. Endophytes are ubiquitous and have been found in all species of plants studied to date; h ...
clavicipitaceous fungus
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from th ...
.
History
Ergoline
alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...
s were first isolated from
ergot
Ergot ( ) or ergot fungi refers to a group of fungi of the genus ''Claviceps''.
The most prominent member of this group is ''Claviceps purpurea'' ("rye ergot fungus"). This fungus grows on rye and related plants, and produces alkaloids that ca ...
, a fungus that infects rye and causes
ergotism or St. Anthony's fire. Reports of the toxic effects due to ergoline alkaloids date back to the 12th century.
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.
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".
Attempts to characterize the activity of ergoline alkaloids began in 1907, with the isolation of ergotoxine by G. Barger and F. H. Carrin.
However, the industrial production of ergot alkaloids didn't begin until 1918, when
Arthur Stoll
Arthur Stoll (8 January 1887 – 13 January 1971) was a Swiss biochemist.
Education and career
The son of a teacher and school headmaster, he studied chemistry at the ETH Zurich, with a PhD in 1911, where he studied with Richard Willstätter. ...
patented the isolation of
ergotamine tartrate
Ergotamine, sold under the brand names Cafergot (with caffeine) and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural simi ...
, which was marketed by
Sandoz
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
in 1921. Following the determination of the basic
chemical structure
A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of at ...
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.
The company, now renamed
Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
, still retains its leadership in the product of ergot alkaloids. In 1943, Arthur Stoll and
Albert Hofmann
Albert Hofmann (11 January 1906 – 29 April 2008) was a Swiss chemist known for being the first to synthesize, ingest, and learn of the psychedelic effects of lysergic acid diethylamide (LSD). Hofmann's team also isolated, named and synthesiz ...
reported the first total synthesis of an ergot alkaloid, ergometrine. 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
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vessel ...
, the treatment of
migraine
Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...
s, and treatment of
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
. 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. 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
Ergometrine, also known as ergonovine and sold under the brand names Ergotrate, Ergostat, and Syntometrine among others, is a medication used to cause contractions of the uterus to treat heavy vaginal bleeding after childbirth. It can be used ei ...
, an ergoline derivative found in ergot, which is a powerful
oxytocic
A uterotonic, also known as ecbolic, are pharmacological agents used to induce contraction or greater tonicity of the uterus. Uterotonics are used both to induce labor and to reduce postpartum hemorrhage.
Labor induction in the third trimester of ...
. From this,
methergine
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 in the treatment of migraine. It reportedly produ ...
, a synthetic derivative, was elucidated.
While used to facilitate child birth, ergoline derivatives can pass into
breast milk
Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates ( lacto ...
and should not be used during breastfeeding.
[kidsgrowth.org --> Drugs and Other Substances in Breast Milk](_blank)
Retrieved on June 19, 2009. They are uterine contractors that can increase the risk of miscarriage during pregnancy.
Another example of medically relevant ergoline alkaloids is
ergotamine
Ergotamine, sold under the brand names Cafergot (with caffeine) and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural simil ...
, an alkaloid also found in ergot. It acts as a
vasoconstrictor
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vess ...
and has been reported to control
migraine
Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...
s. From ergotamine, the
anti-migraine drugs
dihydroergotamine and
methysergide
Methysergide, sold under the brand names Deseril and Sansert, is a monoaminergic medication of the ergoline and lysergamide groups which is used in the prophylaxis and treatment of migraine and cluster headaches. It has been withdrawn from the ma ...
were developed by Albert Hofmann.
Ergoline derivatives, such as
hydergine
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 ( dihydroergocristine, dihydroergocornine, and a ...
, 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
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
has also been prominent. Drugs such as
bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic maligna ...
act as a dopamine receptor
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
, stimulating the nerves that control movement.
Newer synthetic ergoline derivatives that have been synthesized for the treatment of Parkinson's disease include
pergolide
Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Parkinson's disease is associated with reduced do ...
and
lisuride
Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth.
Side effects of lis ...
, which both act as dopamine agonists as well.
A famous ergoline derivative is the
psychedelic drug
Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science o ...
LSD
Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
, a
semi-synthetic
Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...
ergoline alkaloid that was discovered by Albert Hofmann. LSD is considered a
Schedule I controlled substance
This is the list of Schedule I drugs as defined by the United States Controlled Substances Act. 21 CFRbr>1308.11(CSA Sched I) with changes through (Oct 18, 2012). Retrieved September 6, 2013. The following findings are required for drugs to be pl ...
.
Ergometrine
Ergometrine, also known as ergonovine and sold under the brand names Ergotrate, Ergostat, and Syntometrine among others, is a medication used to cause contractions of the uterus to treat heavy vaginal bleeding after childbirth. It can be used ei ...
and
ergotamine
Ergotamine, sold under the brand names Cafergot (with caffeine) and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural simil ...
are included as schedule I precursors in the
.
[http://www.incb.org/pdf/e/list/red.pdf .]
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
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate d ...
,
antidopaminergic
A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have ...
,
serotonergic
Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...
, and
antiserotonergic.
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
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
and
pituitary gland
In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...
to inhibit the
secretion 440px
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
of
prolactin
Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pit ...
.
Drugs such as
bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic maligna ...
interact with the dopaminergic receptor sites as agonists with selectivity for D
2 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.
Antidopaminergic ergolines have found use in
antiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may ...
s and in the treatment of
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
. These substances are
neuroleptic
Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...
and are either an antagonist of dopamine at the postsynaptic level at the D
2 receptor site or an agonist of dopamine at the presynaptic level at the D
1 receptor site.
The antagonist or agonist behavior of the ergolines are substrate dependent and mixed agonist/antagonist behaviors of ergoline derivatives have been reported.
Serotonergic/antiserotonergic
The primary challenges of developing serotonergic/antiserotonergic ergolines is attributed to
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
, 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
Metergoline (, ), also known as methergoline and sold under the brand names Contralac (veterinary) and Liserdol (clinical), is a monoaminergic medication of the ergoline group which is used as a prolactin inhibitor in the treatment of hyperprola ...
, a 5-HT
1A agonist/5-HT
2A antagonist, and
mesulergine
Mesulergine () (developmental code name CU-32085) is a drug of the ergoline group which was never marketed. It acts on serotonin and dopamine receptors. Specifically, it is an agonist of dopamine D2-like receptors and serotonin 5-HT6 receptors ...
, a 5-HT
2A/2C antagonist.
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.
This methodology has been used to develop selective 5-HT
1A and 5-HT
2A ergolines in particular.
Ergoline derivatives
There are 3 main classes of ergoline derivatives, the water-soluble
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
s of ''
lysergic acid
Lysergic acid, also known as -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'' ...
'', the water-insoluble ''ergopeptines'' (i.e., ''ergo
peptides
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
''), and the ''clavine'' group.
Lysergic acid amides
*
Ergine
Ergine, also known as d-lysergic acid amide (LSA) and d-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, Hawai ...
(LSA,
D-lysergic acid amide, LAA, LA-111)
**
IUPAC name
In chemical nomenclature, a preferred IUPAC name (PIN) is a unique name, assigned to a chemical substance and preferred among the possible names generated by IUPAC nomenclature. The "preferred IUPAC nomenclature" provides a set of rules for cho ...
: 9,10-didehydro-6-methylergoline-8beta-carboxamide
**
CAS number
A CAS Registry Number (also referred to as CAS RN or informally CAS Number) is a unique identification number assigned by the Chemical Abstracts Service (CAS), US to every chemical substance described in the open scientific literature. It inclu ...
:
*
Ergonovine
Ergometrine, also known as ergonovine and sold under the brand names Ergotrate, Ergostat, and Syntometrine among others, is a medication used to cause contractions of the uterus to treat heavy vaginal bleeding after childbirth. It can be used ei ...
(ergobasine)
**
INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
: ergometrine
** IUPAC name: (8beta(S))-9,10-didehydro-N-(2-hydroxy-1-methylethyl)-6-methyl-ergoline-8-carboxamide
** CAS number:
*
Methergine
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 in the treatment of migraine. It reportedly produ ...
(ME-277)
** INN: methylergometrine
** IUPAC name: (8beta(S))-9,10-didehydro-N-(1-(hydroxymethyl)propyl)-6-methyl-ergoline-8-carboxamide
** CAS number:
*
Methysergide
Methysergide, sold under the brand names Deseril and Sansert, is a monoaminergic medication of the ergoline and lysergamide groups which is used in the prophylaxis and treatment of migraine and cluster headaches. It has been withdrawn from the ma ...
(UML-491)
** INN: methysergide
** IUPAC name: (8''beta'')-9,10-didehydro-''N''-(1-(hydroxymethyl)propyl)-1,6-dimethyl-ergoline-8-carboxamide
** CAS number:
*
LSD
Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
(
D-lysergic acid diethylamide, LSD-25)
** INN: lysergide
** IUPAC name: (8beta)-9,10-didehydro-N,N-diethyl-6-methyl-ergoline-8-carboxamide
** CAS number:
*
LSH
lsh is a free software implementation of the Secure Shell (SSH) protocol version 2, by the GNU Project including both server and client programs. Featuring Secure Remote Password protocol (SRP) as specified in secsh-srp besides, public-key au ...
(
D-lysergic acid α-hydroxyethylamide)
** IUPAC name: 9,10-didehydro-N-(1-hydroxyethyl)-6-methylergoline-8-carboxamide
** CAS number:
The relationship between these compounds is summarized in the following
structural formula
The structural formula of a chemical compound is a graphic representation of the molecular structure (determined by structural chemistry methods), showing how the atoms are possibly arranged in the real three-dimensional space. The chemical bondi ...
and table of substitutions.
Peptide alkaloids
Peptide ergot alkaloids or
ergopeptines (also known as ''ergopeptides'') are ergoline derivatives that contain a tri
peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A ...
structure attached to the basic ergoline ring in the same location as the
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
group of the lysergic acid derivatives. This structure consists of
proline
Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...
and two other α-amino acids, linked in an unusual
cyclol
The cyclol hypothesis is the now discredited first structural model of a folded, globular protein, formulated in the 1930s. It was based on the cyclol reaction of peptide bonds proposed by physicist Frederick Frank in 1936, in which two pe ...
formation >N-C(OH)< with the carboxyl carbon of proline, at the juncture between the two
lactam
A lactam is a cyclic amide, formally derived from an amino alkanoic acid. The term is a portmanteau of the words ''lactone'' + ''amide''.
Nomenclature
Greek prefixes in alphabetical order indicate ring size:
* α-Lactam (3-atom rings)
* β-Lacta ...
rings. Some of the important ergopeptines 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
Ergocristine is an ergopeptine and one of the ergot alkaloids. As of February 24, 2010 ergocristine has been federally scheduled. Because of the existing Controlled Substance Act regulatory controls on the LSD precursors lysergic acid, lysergi ...
,
ergocornine
Ergocornine is a crystalline ergopeptine and one of the ergot alkaloids separated from ergotoxine. It is also a dopamine receptor agonist. It was discovered by Albert Hofmann, the Swiss chemist who created LSD
Lysergic acid diethylamide ...
and ergocryptine, the latter being a 2:1 mixture of ''
alpha
Alpha (uppercase , lowercase ; grc, ἄλφα, ''álpha'', or ell, άλφα, álfa) is the first letter of the Greek alphabet. In the system of Greek numerals, it has a value of one. Alpha is derived from the Phoenician letter aleph , whic ...
''- and
''beta''-ergocryptine.
* Ergotoxine group (
valine
Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- carboxylic acid group (which is in the deprotonat ...
as the amino acid attached to the ergoline moiety, at R
2 below)
**
Ergocristine
Ergocristine is an ergopeptine and one of the ergot alkaloids. As of February 24, 2010 ergocristine has been federally scheduled. Because of the existing Controlled Substance Act regulatory controls on the LSD precursors lysergic acid, lysergi ...
***
IUPAC name
In chemical nomenclature, a preferred IUPAC name (PIN) is a unique name, assigned to a chemical substance and preferred among the possible names generated by IUPAC nomenclature. The "preferred IUPAC nomenclature" provides a set of rules for cho ...
: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-(1-methylethyl)-5'-(phenylmethyl)-, (5'-alpha)-
***
CAS number
A CAS Registry Number (also referred to as CAS RN or informally CAS Number) is a unique identification number assigned by the Chemical Abstracts Service (CAS), US to every chemical substance described in the open scientific literature. It inclu ...
:
**
Ergocornine
Ergocornine is a crystalline ergopeptine and one of the ergot alkaloids separated from ergotoxine. It is also a dopamine receptor agonist. It was discovered by Albert Hofmann, the Swiss chemist who created LSD
Lysergic acid diethylamide ...
*** IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2',5'-bis(1-methylethyl)-, (5'-alpha)-
*** CAS number:
** ''alpha''-
Ergocryptine
Ergocryptine is an ergopeptine and one of the ergot alkaloids. It is isolated from ergot or fermentation broth and it serves as starting material for the production of bromocriptine.
Chemistry
Ergocryptine is a mixture of two very similar compou ...
*** IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)-, (5'alpha)-
*** CAS number:
**
''beta''-Ergocryptine
*** IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-(1-methylethyl)-5'-(1-methylpropyl)-, (5'alpha(''S''))-
*** CAS number:
* Ergotamine group (
alanine
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side c ...
at R
2)
**
Ergotamine
Ergotamine, sold under the brand names Cafergot (with caffeine) and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural simil ...
*** IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-methyl-5'-(phenylmethyl)-, (5'-alpha)-
*** CAS number:
**
Ergovaline
Ergovaline is an ergopeptine and one of the ergot alkaloids. It is usually found in endophyte-infected species of grass like Tall fescue or Perennial Ryegrass. It is toxic to cattle feeding on infected grass, probably because it acts as a vasoco ...
*** IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-methyl-5'-(1-methylethyl)-, (5'alpha)-
*** CAS number:
** ''alpha''-
Ergosine
*** IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-methyl-5'-(2-methylpropyl)-, (5'-alpha)-
*** CAS number:
**
''beta''-Ergosine
*** IUPAC name: Ergotaman-3',6',18-trione, 12'-hydroxy-2'-methyl-5'-(1-methylpropyl)-, (5'-alpha(''S''))-
*** CAS number:
Clavines
A variety of modifications to the basic ergoline are seen in nature, for example
agroclavine
Agroclavine belongs to the group of ergot alkaloids, such as ergotamine
Ergotamine, sold under the brand names Cafergot (with caffeine) and Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally a ...
,
elymoclavine
Elymoclavine is an ergot alkaloid (ergoline alkaloid). It can be produced from ''C. fusiformis'' from ''Pennisetum typhoideum''. It is a precursor in the biosynthesis of lysergic acid, D-(+)-lysergic acid. Ergot alkaloids are natural products deri ...
,
lysergol
Lysergol is an alkaloid of the ergoline family that occurs as a minor constituent in some species of fungi (most within ''Claviceps''), and in the morning glory family of plants (Convolvulaceae), including the Psychedelics, dissociatives and deli ...
. 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:
*
Cabergoline
Cabergoline, sold under the brand name Dostinex among others, is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications. It is taken by mouth.
Cabergoline is an e ...
(
INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
)
**
IUPAC name
In chemical nomenclature, a preferred IUPAC name (PIN) is a unique name, assigned to a chemical substance and preferred among the possible names generated by IUPAC nomenclature. The "preferred IUPAC nomenclature" provides a set of rules for cho ...
: 1-
6-Allylergolin-8β-yl)-carbonyl1-
-(dimethylamino)propyl3-ethylurea
**
CAS number
A CAS Registry Number (also referred to as CAS RN or informally CAS Number) is a unique identification number assigned by the Chemical Abstracts Service (CAS), US to every chemical substance described in the open scientific literature. It inclu ...
:
*
Pergolide
Pergolide, sold under the brand name Permax and Prascend (veterinary) among others, is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinson's disease. Parkinson's disease is associated with reduced do ...
(INN)
** IUPAC name: (8β)-8-((methylthio)methyl)-6-propyl-ergoline
** CAS number:
*
Lisuride
Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth.
Side effects of lis ...
(INN)
** IUPAC name: 3-(9,10-didehydro-6-methylergolin-8α-yl)-1,1-diethylurea
** CAS number:
See also
*
Ergotism
*
Ergot
Ergot ( ) or ergot fungi refers to a group of fungi of the genus ''Claviceps''.
The most prominent member of this group is ''Claviceps purpurea'' ("rye ergot fungus"). This fungus grows on rye and related plants, and produces alkaloids that ca ...
*
LSD
Lysergic acid diethylamide (LSD), also known colloquially as acid, is a potent psychedelic drug. Effects typically include intensified thoughts, emotions, and sensory perception. At sufficiently high dosages LSD manifests primarily mental, vi ...
*
Ergine
Ergine, also known as d-lysergic acid amide (LSA) and d-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, Hawai ...
*
Migraine
Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...
*
Albert Hofmann
Albert Hofmann (11 January 1906 – 29 April 2008) was a Swiss chemist known for being the first to synthesize, ingest, and learn of the psychedelic effects of lysergic acid diethylamide (LSD). Hofmann's team also isolated, named and synthesiz ...
References
External links
The Ergot Alkaloids (A. T. Sneden)The Psychoactive Ergot Alkaloids and their occurrence in the Microfungi — M. P. Bock and D. G. ParberyHofmann, A. ''Teonanácatl and Ololiuqui, two ancient magic drugs of Mexico'' Bulletin on Narcotics 1971 1 3TiHKAL (A & A Shulgin) #26
{{Ergolines
Tryptamine alkaloids
Quinoline alkaloids
Alkaloids found in fungi