Bromocriptine
Encyclopedia
Bromocriptine an ergoline
derivative, is a dopamine agonist
that is used in the treatment of pituitary tumors, Parkinson's disease
(PD), hyperprolactinaemia
, neuroleptic malignant syndrome
, and type 2 diabetes
.
, galactorrhea
, hypogonadism
, and acromegaly
may all be caused by pituitary problems, such as hyperprolactinaemia
, and therefore, these problems may be treated by this drug. In 2009, bromocriptine mesylate was approved by the FDA for treatment of type 2 diabetes under the trade name Cycloset (VeroScience). It is currently unknown how this drug improves glycemic control, but it has been shown to reduce HbA1c by ~0.5 percentage points.
D2 receptors and various serotonin
receptors. It also inhibits the release of glutamate, by reversing the glutamate GLT1 transporter.
Bromocriptine use has been anecdotically associated with causing or worsening psychotic
symptoms (its mechanism is in opposition of most antipsychotics, whose mechanisms generally block dopamine).
Pulmonary fibrosis has been reported when bromocriptine was used in high doses for the treatment of Parkinson's disease.
, bromocriptine is a cyclol
; two peptide groups of its tripeptide
moiety are crosslinked, forming the >N-C(OH)< juncture between the two rings with the amide
functionality
.
Bromocriptine, 2-bromoergocriptine, is a semisynthetic
derivative of a natural ergot
alkaloid
, ergocriptin (a derivative of lysergic acid
), which is synthesized
by bromination of ergocriptin using N-bromosuccinimide
.
Ergoline
Ergoline is a chemical compound whose structural skeleton is contained in a diverse range of alkaloids including a few psychedelic drugs . Ergoline derivatives are used clinically for the purpose of vasoconstriction and in the treatment of migraines and Parkinson's disease...
derivative, is a dopamine agonist
Dopamine agonist
A dopamine agonist is a compound that activates dopamine receptors in the absence of dopamine. Dopamine agonists activate signaling pathways through the dopamine receptor and trimeric G-proteins, ultimately leading to changes in gene transcription.-Uses:...
that is used in the treatment of pituitary tumors, Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
(PD), hyperprolactinaemia
Hyperprolactinaemia
Hyperprolactinaemia or hyperprolactinemia is the presence of abnormally-high levels of prolactin in the blood. Normal levels are less than 500 mIU/L for women, and less than 450 mIU/L for men....
, neuroleptic malignant syndrome
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...
, and type 2 diabetes
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
.
Indications
Amenorrhea, female infertilityInfertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
, galactorrhea
Galactorrhea
Galactorrhea or galactorrhoea is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing.Contemporary Maternal-Newborn Nursing Care defines galactorrhea as "nipple discharge." -Causes:...
, hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
, and acromegaly
Acromegaly
Acromegaly is a syndrome that results when the anterior pituitary gland produces excess growth hormone after epiphyseal plate closure at puberty...
may all be caused by pituitary problems, such as hyperprolactinaemia
Hyperprolactinaemia
Hyperprolactinaemia or hyperprolactinemia is the presence of abnormally-high levels of prolactin in the blood. Normal levels are less than 500 mIU/L for women, and less than 450 mIU/L for men....
, and therefore, these problems may be treated by this drug. In 2009, bromocriptine mesylate was approved by the FDA for treatment of type 2 diabetes under the trade name Cycloset (VeroScience). It is currently unknown how this drug improves glycemic control, but it has been shown to reduce HbA1c by ~0.5 percentage points.
Pharmacology
Bromocriptine is a potent agonist at dopamineDopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
D2 receptors and various serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
receptors. It also inhibits the release of glutamate, by reversing the glutamate GLT1 transporter.
Side effects
Most frequent side effects are nausea, orthostatic hypotension, headaches and vomiting through stimulation of the brainstem vomiting centre. Bromocriptine can cause worsening of liver problems. Vasospasms with serious consequences such as myocardial infarction and stroke have been reported in connection with the puerperium, appears to be extremely rare event.Bromocriptine use has been anecdotically associated with causing or worsening psychotic
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
symptoms (its mechanism is in opposition of most antipsychotics, whose mechanisms generally block dopamine).
Pulmonary fibrosis has been reported when bromocriptine was used in high doses for the treatment of Parkinson's disease.
Chemistry
Like all ergopeptidesErgoline
Ergoline is a chemical compound whose structural skeleton is contained in a diverse range of alkaloids including a few psychedelic drugs . Ergoline derivatives are used clinically for the purpose of vasoconstriction and in the treatment of migraines and Parkinson's disease...
, bromocriptine is a cyclol
Cyclol
The cyclol hypothesis is the first structural model of a folded, globular protein. It was developed by Dorothy Wrinch in the late 1930s, and was based on three assumptions. Firstly, the hypothesis assumes that two peptide groups can be crosslinked by a cyclol reaction ; these crosslinks are...
; two peptide groups of its tripeptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
moiety are crosslinked, forming the >N-C(OH)< juncture between the two rings with the amide
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
functionality
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
.
Bromocriptine, 2-bromoergocriptine, is a semisynthetic
Semisynthetic
"Semisynthesis" or partial chemical synthesis is a type of chemical synthesis that uses compounds isolated from natural sources as starting materials. These natural biomolecules are usually large and complex molecules...
derivative of a natural ergot
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. This fungus grows on rye and related plants, and produces alkaloids that can cause ergotism in humans and other mammals who consume grains contaminated with its...
alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
, ergocriptin (a derivative of lysergic acid
Lysergic acid
Lysergic acid, also known as D-lysergic acid and -lysergic acid, is a precursor for a wide range of ergoline alkaloids that are produced by the ergot fungus and some plants. Amides of lysergic acid, lysergamides, are widely used as pharmaceuticals and as psychedelic drugs...
), which is synthesized
by bromination of ergocriptin using N-bromosuccinimide
N-Bromosuccinimide
N-Bromosuccinimide or NBS is a chemical reagent which is used in radical substitution and electrophilic addition reactions in organic chemistry. NBS can be considered a convenient source of cationic bromine.-Preparation:...
.
- E. Fluckiger, A. Hoffmann, (1973).
- A. Hofman, E. Flueckiger, (1969).
External links
- www.AcromegalyCommunity.com: Emotional and communal support for those touched by Acromegaly- page discussing drug, side effects, and prescription programs
- http://www.drugs.com/pro/bromocriptine.html