Definition
Description
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Hepatic, extensively metabolized. The known urinary metabolites are: a-methyldopa mono-0-sulfate; 3-0-methyl-a-methyldopa; 3,4-dihydroxyphenylacetone; a-methyldopamine; 3-0-methyl-a-methyldopamine and their conjugates. Route of Elimination: Methyldopa is extensively metabolized. The known urinary metabolites are: alpha-methyldopa mono-O-sulfate; 3-0-methyl-alpha-methyldopa; 3,4-dihydroxyphenylacetone; alpha-methyldopamine; 3-0-methyl-alpha-methyldopamine and their conjugates. Approximately 70 percent of the drug which is absorbed is excreted in the urine as methyldopa and its mono-O-sulfate conjugate. Methyldopa crosses the placental barrier, appears in cord blood, and appears in breast milk. Half Life: The plasma half-life of methyldopa is 105 minutes.
- Uses/Sources: For use in the treatment of hypertension (A308).
- Health Effects: Acute overdosage may produce acute hypotension with other responses attributable to brain and gastrointestinal malfunction. Haemolytic anaemia, bone marrow suppression, and parkinsonism may also occur (RxList A308, L1178).
- Symptoms: Excessive sedation, weakness, bradycardia, dizziness, lightheadedness, bloating, constipation, distention, flatus, diarrhea, nausea, vomiting and severely low blood pressure (RxList A308).
- Treatment: In the event of overdosage, symptomatic and supportive measures should be employed. When ingestion is recent, gastric lavage or emesis may reduce absorption. When ingestion has been earlier, infusions may be helpful to promote urinary excretion. Otherwise, management includes special attention to cardiac rate and output, blood volume, electrolyte balance, paralytic ileus, urinary function and cerebral activity (A308).
- Route of Exposure: Oral (A308). Absorption from the gastrointestinal tract is variable but averages approximately 50%.
Toxicity
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: >1.5 g/kg (Oral, Mouse) (A308) LD50: >1.5 g/kg (Oral, Rat) (A308)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Estrogen receptor beta Solute carrier family 15 member 1 |
10052994 17145705 |
|
Aromatic-L-amino-acid decarboxylase | Alpha-methyldopa is a competitive inhibitor of the enzyme aromatic L-amino acid decarboxylase, which converts L-DOPA into dopamine. Dopamine is a precursor for norepinephrine (noradrenaline) and subsequently epinephrine (adrenaline). This inhibition results in reduced dopaminergic and adrenergic neurotransmission in the peripheral nervous system. This effect may lower blood pressure and cause central nervous system effects such as depression, anxiety, apathy, anhedonia, and parkinsonism. In addition, decreased dopamine may reduce its inhibitory effect on prolactin leading to signs and symptoms of hyperprolactinemia. |
13189588 |
Alpha-2A adrenergic receptor | Although the mechanism of action has yet to be conclusively demonstrated, the antihypertensive effect of methyldopa probably is due to its metabolism to alpha-methylnorepinephrine, which then lowers arterial pressure by stimulation of central inhibitory alpha-adrenergic receptors, false neurotransmission, and/or reduction of plasma renin activity. Methyldopa has been shown to cause a net reduction in the tissue concentration of serotonin, dopamine, norepinephrine, and epinephrine. |
17485976 10415926 9284427 1363322 14557373 8743022 |
Methyldopa Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Non-alcoholic fatty liver disease | 7.37 |
|
Pheochromocytoma | 6.97 |
|
Amphetamine-Related Disorders | 6.62 | |
Autism | 6.02 |
|
Aromatic amino acid decarboxylase deficiency | 5.84 |
|
Oculocutaneous albinism type 1 | 5.79 |
|
Oculocutaneous albinism type 1B | 5.79 |
|
Hyperuricemic Nephropathy, Familial Juvenile 2 | 5.64 |
|
Albinism, Oculocutaneous | 5.45 |
|
Parkinson's disease | 5.27 |
|
Albinism ocular late onset sensorineural deafness | 5.25 |
|
Fetal Growth Retardation | 5.2 |
|
Musculoskeletal Pain | 5.07 |
|
Allanson Pantzar McLeod syndrome | 4.95 |
|
RENAL TUBULAR DYSGENESIS | 4.95 |
|
Chromosome Aberrations | 4.9 |
|
DiGeorge Syndrome | 4.81 |
|
HEARING LOSS, CISPLATIN-INDUCED, SUSCEPTIBILITY TO | 4.81 |
|
Liddle Syndrome | 4.75 |
|
Temporomandibular joint disorder | 4.65 |
|