Repositioning Candidate Details
| Candidate ID: | R0283 |
| Source ID: | DB00968 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Methyldopa |
| Synonyms: | |
| Molecular Formula: | C10H13NO4 |
| SMILES: | C[C@](N)(CC1=CC=C(O)C(O)=C1)C(O)=O |
| Structure: |
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| DrugBank Description: | An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent. [PubChem] |
| CAS Number: | 555-30-6 |
| Molecular Weight: | 211.2145 |
| DrugBank Indication: | For use in the treatment of hypertension. |
| DrugBank Pharmacology: | Methyldopa is an aromatic-amino-acid decarboxylase inhibitor in animals and in man. Only methyldopa, the <i>L</i>-isomer of alpha-methyldopa, has the ability to inhibit dopa decarboxylase and to deplete animal tissues of norepinephrine. In man the antihypertensive activity appears to be due solely to the L-isomer. About twice the dose of the racemate (DL-alpha-methyldopa) is required for equal antihypertensive effect. Methyldopa has no direct effect on cardiac function and usually does not reduce glomerular filtration rate, renal blood flow, or filtration fraction. Cardiac output usually is maintained without cardiac acceleration. In some patients the heart rate is slowed. Normal or elevated plasma renin activity may decrease in the course of methyldopa therapy. Methyldopa reduces both supine and standing blood pressure. Methyldopa usually produces highly effective lowering of the supine pressure with infrequent symptomatic postural hypotension. Exercise hypotension and diurnal blood pressure variations rarely occur. |
| DrugBank MoA: | Although the mechanism of action has yet to be conclusively demonstrated, the resultant hypotensive effect is most likely due to the drug's action on the CNS. Methyldopa is converted into the metabolite, alpha-methylnorepinephrine, in the CNS, where it stimulates the central inhibitory alpha-adrenergic receptors, leading to a reduction in sympathetic tone, total peripheral resistance, and blood pressure. Reduction in plasma renin activity, as well as the inhibition of both central and peripheral norepinephrine and serotonine production may also contribute to the drug's antihypertensive effect, although this is not a major mechanism of action. This is done through the inhibition of the decarboxylation of dihydroxyphenylalanine (dopa)—the precursor of norepinephrine—and of 5-hydroxytryptophan (5-HTP)—the precursor of serotonin—in the CNS and in most peripheral tissues. |
| Targets: | Aromatic-L-amino-acid decarboxylase; Alpha-2A adrenergic receptor |
| Inclusion Criteria: |
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