3626 Methyldopa Methyldopa or alpha-methyldopa (brand names Aldomet, Apo-Methyldopa, Dopamet, Novomedopa) is a centrally-acting adrenergic antihypertensive medication. Its use is now deprecated following introduction of alternative safer classes of agents. However it continues to have a role in otherwise difficult to treat hypertension and gestational hypertension (formerly known as pregnancy-induced hypertension). 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. Methyldopa, in its active metabolite form, is a central alpha-2 receptor agonist. Using methyldopa leads to alpha-2 receptor-negative feedback to sympathetic nervous system (SNS) (centrally and peripherally), allowing peripheral sympathetic nervous system tone to decrease. Such activity leads to a decrease in total peripheral resistance (TPR) and cardiac output. When introduced it was a mainstay of antihypertensive therapy, but its use has declined, with increased use of other safer classes of agents. One of its important present-day uses is in the management of pregnancy-induced hypertension, as it is relatively safe in pregnancy compared to other antihypertensive drugs (Wikipedia). 555-30-6 38853 C10H13NO4 211.084460 White to yellowish white, odorless fine powder. Also appear as a colorless or almost colorless crystal (RxList A308, L1179). 300°C 10mg/mL at 25°C Oral (A308). Absorption from the gastrointestinal tract is variable but averages approximately 50%. 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. 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. LD50: >1.5 g/kg (Oral, Mouse) (A308) LD50: >1.5 g/kg (Oral, Rat) (A308) No indication of carcinogenicity to humans (not listed by IARC). For use in the treatment of hypertension (A308). 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). Excessive sedation, weakness, bradycardia, dizziness, lightheadedness, bloating, constipation, distention, flatus, diarrhea, nausea, vomiting and severely low blood pressure (RxList A308). 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). 2009-08-06T22:55:28Z 2016-11-09T01:08:53Z Catechol O-methyltransferase (COMT) (P21964) (A308). http://en.wikipedia.org/wiki/Methyldopa C07194 61058 ALPHA-METHYLDOPA Alpha-methyldopa DB00968 true Catechol O-methyltransferase (P21964) (A308) C[C@](N)(CC1=CC=C(O)C(O)=C1)C(O)=O C10H13NO4 InChI=1S/C10H13NO4/c1-10(11,9(14)15)5-6-2-3-7(12)8(13)4-6/h2-4,12-13H,5,11H2,1H3,(H,14,15)/t10-/m0/s1 CJCSPKMFHVPWAR-JTQLQIEISA-N 211.2145 211.084457909 Exogenous Solid -1.79 HMDB11754 CHEMBL459 35562 <p><a href="http://www.drugsyn.org/Methyldopa.htm">DrugSyn.org</a></p> CHEM002561 (2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid