From Wikipedia,
the free encyclopedia
Chemical structure of
ergoline
Ergoline is a
chemical
compound whose structure
serves as the skeleton for a
diverse range of
alkaloids and
synthetic
drugs. Substances derived from
ergoline are used clinically as
oxytocics and in the treatment
of
migraine and
Parkinson's disease, and are
implicated in the disease
ergotism and in the action of
psychedelic
drugs such as
ololiuhqui and
LSD. Ergometrine and
ergotamine are listed as Table I
precursors under the
United Nations Convention Against
Illicit Traffic in Narcotic Drugs
and Psychotropic Substances[1].
Chemistry
There are three main classes of
ergoline derivatives, the
water-soluble
amides of lysergic acid,
the water-insoluble ergopeptide
alkaloids, and the clavine
group.
Lysergic acid amides
The prototype of this class is
-
Ergine (d-lysergic acid
amide, LSA, LAA, LA-111)
Other important members
include:
- 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: lysergamide
-
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.
| Name |
R1 |
N1 |
N2 |
| ergine |
|
|
|
| ergonovine |
|
CH(CH3)CH2OH |
|
| methergine |
|
CH(CH2CH3)CH2OH |
|
| methysergide |
CH3 |
CH(CH2CH3)CH2OH |
|
|
LSD |
|
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. Some of the
important ergopeptides are
summarized below. In addition to
the following ergopeptides, 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 (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
| Name |
R2 |
R2' |
R5' |
| 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 fall easily into
any of the above groups. Some
examples are:
- Pergolide (INN)
- Lisuride (INN)
History & Uses
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 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, the anti-senility
nootropic (smart drug)
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.
In
1960,
Albert Hofmann (discoverer of
methergine, dihydroergotamine,
Hydergine and LSD) delivered a
speech that was to cause
shockwaves of incredulity and even
disbelief in the scientific
community. Ergoline alkaloids,
previously only known from the
lower
fungi, had been found in two
species of
flowering plants. These were
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".
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
Hawaiian species
Argyreia nervosa was later
found to include similar
alkaloids. It is possible, though
not proven, that
ergine and/or isoergine are
responsible for the
hallucinogenic effects.
