Definition
Description
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Pergolide undergoes extensive first-pass hepatic metabolism and its metabolism are excreted mainly in the urine. (A2932) Route of Elimination: The major route of excretion is the kidney. Half Life: 27 hours
- Uses/Sources: Indicated as adjunctive treatment to levodopa/carbidopa in the management of the signs and symptoms of Parkinson's disease. It was withdrawn from the US and Canadian markets in 2007 due to an increased risk of cardiac valvulopathy. Pergolide is an ergoline-based, long-acting dopamine agonist which is effective in the treatment of Parkinson's disease and hyperprolactinemia. It has also been observed to have antihypertensive effects. Ergoline alkaloids occurs in various species of vines of the Convolvulaceae (morning glory) family and in some species of lower fungi. (L1918, L1929)
- Health Effects: 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. The use of pergolide has been shown to increase the risk of cardiac valvular disease. It also increases the risk of fibrotic complications including pulmonary, pleural, and/or retroperitoneal fibrosis, pericarditis, pleuritis, and pericardial and/or pleural effusions. (A2913, L1570)
- Symptoms: Symptoms of pergolide overdose include nausea, vomiting, convulsions, decreased blood pressure, and CNS stimulation. 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, L1570)
- Treatment: Management of overdosage may require supportive measures to maintain arterial blood pressure. Cardiac function should be monitored; an antiarrhythmic agent may be necessary. If signs of CNS stimulation are present, a phenothiazine or other butvronhenone neuroleptic agent may be indicated; the efficacy of such drugs in reversing the effects of overdose has not been assessed. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. 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, L1930)
- Route of Exposure: Oral (L1929)
Toxicity
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 15 mg/kg (Oral, Rat) (A308)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
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 pergolide use. (A2933) |
18691132 |
D(2) dopamine receptor | Pergolide is a potent dopamine receptor agonist. It directly stimulates post-synaptic dopamine receptors at both D1 and D2 receptor sites in the nigrostriatal system. This can reduce the motor complications associated with Parkinson's. (A365, A2294, A2294, A1783, A2296, A2297, A2934) |
9057850 16842172 3828803 15180131 2860228 10516878 9784114 11752352 1674528 |
D(1A) dopamine receptor | Pergolide is a potent dopamine receptor agonist. It directly stimulates post-synaptic dopamine receptors at both D1 and D2 receptor sites in the nigrostriatal system. This can reduce the motor complications associated with Parkinson's. (A365, A2934) |
15180131 9784114 11752352 |
D(1B) dopamine receptor | Pergolide is a potent dopamine receptor agonist. It directly stimulates post-synaptic dopamine receptors at both D1 and D2 receptor sites in the nigrostriatal system. This can reduce the motor complications associated with Parkinson's. (A2934) |
15180131 |
5-hydroxytryptamine receptor 2A 5-hydroxytryptamine receptor 2C 5-hydroxytryptamine receptor 1A Alpha-1A adrenergic receptor Alpha-2A adrenergic receptor D(3) dopamine receptor D(4) dopamine receptor 5-hydroxytryptamine receptor 1D Alpha-1B adrenergic receptor Alpha-1D adrenergic receptor Alpha-2B adrenergic receptor Alpha-2C adrenergic receptor |
8496900 10641988 9057850 18703043 18691132 1683537 |
Pergolide Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Amphetamine-Related Disorders | 14.26 | |
Glioma | 10.5 |
|
Colonic neoplasm | 10.25 |
|
Cocaine dependence | 8.93 |
|
Diabetes Mellitus, Experimental | 8.92 |
|
Parkinson's disease | 8.86 |
|
Esophageal squamous cell carcinoma | 8.84 |
|
Cell Transformation, Neoplastic | 8.23 |
|
Mesothelioma, Malignant | 8.17 |
|
Schizophrenia | 8.15 |
|
Dyskinesia, Drug-Induced | 8.13 |
|
Esophageal Neoplasms | 7.77 |
|
Kidney Failure, Chronic | 7.74 |
|
Heroin Dependence | 7.71 |
|
Lymphoma, T-Cell, Cutaneous | 7.32 |
|
Heat Stroke | 7.3 |
|
Parkinsonian Disorders | 7.24 |
|
Renal cell carcinoma | 7.07 |
|
Brain Ischemia | 6.95 |
|
Hyperkinesis | 6.85 |
|