Bromocriptine

Bromocriptine (INN; trade names Parlodel, Cycloset), 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.

Indications
Amenorrhea, female infertility, 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.

Pharmacology
Bromocriptine is a potent agonist at dopamine D2 receptors and various serotonin receptors. It also inhibits the release of glutamate, by reversing the glutamate GLT-1 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 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 ergopeptides, 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.


 * E. Fluckiger, A. Hoffmann, (1973).
 * A. Hofman, E. Flueckiger, (1969).