Description
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Hepatic. Cabergoline is extensively metabolized, predominately via hydrolysis of the acylurea bond of the urea moiety. Cytochrome P-450 mediated metabolism appears to be minimal. The main metabolite identified in urine is 6-allyl-8b-carboxy-ergoline (4-6% of dose). Three other metabolites were identified urine (less than 3% of dose). Route of Elimination: After oral dosing of radioactive cabergoline to five healthy volunteers, approximately 22% and 60% of the dose was excreted within 20 days in the urine and feces, respectively. Less than 4% of the dose was excreted unchanged in the urine. Half Life: The elimination half-life is estimated from urinary data of 12 healthy subjects to range between 63 to 69 hours.
- Uses/Sources: For the treatment of hyperprolactinemic disorders, either idiopathic or due to prolactinoma (prolactin-secreting adenomas). May also be used to manage symptoms of Parkinsonian Syndrome as monotherapy during initial symptomatic management or as an adjunct to levodopa therapy during advanced stages of disease. Cabergoline is frequently used as a second-line agent in the management of prolactinomas when bromocriptine is ineffective. Ergoline alkaloids occurs in various species of vines of the Convolvulaceae (morning glory) family and in some species of lower fungi. (L1918, L1935)
- Health Effects: Cabergoline use may cause valvular heart disease and fibrosis. Ingestion of ergoline alkaloids is known to cause the disease ergotism. Ergotism occurs in two forms, gangrenous and convulsive, likely depending on the different kinds and amounts of ergoline alkaloids present. (A2913, L1935, L1936)
- Symptoms: Side effects of cabergoline include nausea, constipation, dry mouth, sleep disturbances, vertigo, depression, hypotension, and peripheral edema. Convulsive ergotism can cause painful seizures and spasms, diarrhea, paresthesias, itching, headaches, nausea and vomiting. Usually the gastrointestinal effects precede the central nervous system effects. As well as seizures there can be hallucinations and mental effects including mania or psychosis. Gangrenous ergotism causes dry gangrene as a result of vasoconstriction induced in the more poorly vascularized distal structures, such as the fingers and toes. Symptoms include desquamation, weak periphery pulse, loss of peripheral sensation, edema and ultimately the death and loss of affected tissues. (L1920, L1936) Overdosage might be expected to produce nasal congestion, syncope, or hallucinations.
- Treatment: Treatment for ergotism consists of vasodilators, anticoagulants and low molecular weight dextrans. If necessary, a sympathetic nerve blockade may be carried out, such as brachial plexus blockade. Temporary sedation (e.g. haloperidol) will be necessary in hallucination and diazepam is used for convulsions. There is no specific antidote. (L1921)
- Route of Exposure: Oral (L1935) First-pass effect is seen, however the absolute bioavailability is unknown.
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
5-hydroxytryptamine receptor 2A 5-hydroxytryptamine receptor 2C 5-hydroxytryptamine receptor 1A Alpha-1A adrenergic receptor Alpha-2A adrenergic receptor 5-hydroxytryptamine receptor 7 D(3) dopamine receptor D(4) dopamine receptor 5-hydroxytryptamine receptor 1D D(1A) dopamine receptor Alpha-1B adrenergic receptor Alpha-1D adrenergic receptor Alpha-2B adrenergic receptor D(1B) dopamine receptor Beta-1 adrenergic receptor Beta-2 adrenergic receptor Alpha-2C adrenergic receptor D(1) dopamine receptor D(2S) dopamine receptor D(2L) dopamine receptor |
12388667 20426763 11436517 12388666 16982285 18691132 10641988 18992242 |
|
5-hydroxytryptamine receptor 2B 5-hydroxytryptamine receptor 1B |
Agonism of 5-HT2B and 5-HT1B receptors is believed to be responsible for the fibrotic reactions and cardiac valvular disease associated with cabergoline use. (A2933) |
18691132 |
D(2) dopamine receptor | Cabergoline is a long-acting dopamine receptor agonist with a high affinity for D2 receptors. This agonism has an anti-Parkinsonian effect. (A2946) |
14523624 |
Cabergoline Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Cocaine dependence | 19.05 |
|
Parkinsonian Disorders | 16.53 |
|
Dyskinesia, Drug-Induced | 14.15 |
|
Amphetamine-Related Disorders | 13.69 | |
Parkinson's disease | 11.56 |
|
Movement disorder | 11.15 |
|
Pituitary Neoplasms | 8.87 |
|
Heroin Dependence | 8.86 |
|
Disruptive, Impulse Control, and Conduct Disorders | 7.78 |
|
Hypotension | 7.65 |
|
Hyperprolactinemia | 7.57 |
|
Dyskinesias | 7.29 |
|
Hyperkinesis | 6.87 |
|
Catalepsy | 6.82 |
|
Neurodegenerative Diseases | 6.76 |
|
Basal Ganglia Diseases | 6.5 |
|
Spinocerebellar ataxia 23 | 6.5 |
|
Bradycardia | 6.45 |
|
Hyperalgesia | 6.43 |
|
Seizures | 5.91 |
|