Bromocriptine

Updated on Oct 11, 2024

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Trade names Parlodel, Brotin Routes ofadministration oral, intravenous CAS ID 25614-03-3		MedlinePlus a682079 Molar mass 654.595 g/mol

AHFS/Drugs.com Monograph,International Drug Names Pregnancycategory AU: AUS: B (No risk in non-human studies) ATC code G02CB01 (WHO) N04BC01 (WHO)

Ivf med bromocriptine

Bromocriptine (INN; trade names Parlodel, Cycloset, Brotin (Pakistan)), 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 with this drug. Bromocriptine has completely treated gestational macromastia eliminating the need for reduction surgery, in a recent case. It has also been used in treating nonpuerperal mastitis. Since the late 1980s it has been used, off-label, to reduce the symptoms of cocaine withdrawal. 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 GLT1 transporter.

Bromocriptine agonizes the following monoamine receptors:

Dopamine D₁ family

D₁ (K_i=682 nM)

D₅ (K_i=496 nM)

Dopamine D₂ family

D₂ (K_i=2.96 nM)

D₃ (K_i=5.42 nM)

D₄ (K_i=328 nM)

Serotonin 5-HT

5-HT_1A (K_i=12.9 nM)

5-HT_1B (K_i=355 nM)

5-HT_1D (K_i=10.7 nM)

5-HT_2A (K_i=107 nM)

5-HT_2B (K_i=56.2 nM)

5-HT_2C (K_i=741 nM)

5-HT₆ (K_i=33 nM)

Adrenergic α family

α_1A (K_i=4.17 nM)

α_1B (K_i=1.38 nM)

α_1D (K_i=1.12 nM)

α_2A (K_i=11.0 nM)

α_2B (K_i=34.7 nM)

α_2C (K_i=28.2 nM)

Adrenergic β family

β₁ (K_i=589 nM)

β₂ (K_i=741 nM)

Side effects

Most frequent side effects are nausea, orthostatic hypotension, headaches, and vomiting through stimulation of the brainstem vomiting centre. Vasospasms with serious consequences such as myocardial infarction and stroke that have been reported in connection with the puerperium, appear to be extremely rare events. Peripheral vasospasm (of the fingers or toes) can cause Raynaud's Phenomenon. Bromocriptine use has been anecdotally 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.

Use to suppress milk production after childbirth was reviewed in 2014 and it was concluded that in this context a causal association with serious cardiovascular, neurological or psychiatric events could not be excluded with an overall incidence rate estimated to range between 0.005% and 0.04%. Additional safety precautions and stricter prescribing rules were suggested based on the data. Bile salt export pump inhibitor.

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 is a semisynthetic derivative of a natural ergot alkaloid, ergocryptine (a derivative of lysergic acid), which is synthesized by bromination of ergocryptine using N-bromosuccinimide.

References

Bromocriptine Wikipedia

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