| DrugBank Indication: |
For the treatment of galactorrhea due to hyperprolactinemia, prolactin-dependent menstrual disorders and infertility, prolactin-secreting adenomas, prolactin-dependent male hypogonadism, as adjunct therapy to surgery or radiotherapy for acromegaly or as monotherapy is special cases, as monotherapy in early Parksinsonian Syndrome or as an adjunct with levodopa in advanced cases with motor complications. Bromocriptine has also been used off-label to treat restless legs syndrome and neuroleptic malignant syndrome.
|
| DrugBank Pharmacology: |
Bromocriptine stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D<sub>1</sub> and D<sub>5</sub> subreceptors, which are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D<sub>2</sub>, D<sub>3</sub> and D<sub>4</sub> subreceptors, which are associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D<sub>2</sub> and D<sub>3</sub> receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D<sub>2</sub> stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D<sub>2</sub> stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D<sub>2</sub>-receptors. It also exhibits agonist activity (in order of decreasing binding affinity) on 5-hydroxytryptamine (5-HT)<sub>1D</sub>, dopamine D<sub>3</sub>, 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>1B</sub>, and 5-HT<sub>2C</sub> receptors, antagonist activity on α<sub>2A</sub>-adrenergic, α<sub>2C</sub>, α<sub>2B</sub>, and dopamine D<sub>1</sub> receptors, partial agonist activity at receptor 5-HT<sub>2B</sub>, and inactivates dopamine D<sub>4</sub> and 5-HT<sub>7</sub> receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT<sub>2A</sub> agonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion making bromocriptine an effective agent for treating disorders associated with hypersecretion of prolactin. Pulmonary fibrosis may be associated bromocriptine’s agonist activity at 5-HT<sub>1B</sub> and 5-HT<sub>2B</sub> receptors.
|
