Aldoclor-150;Aldoclor-250;Aldomet;Aldometil;Aldomin;Aldoril 15;Aldoril 25;Aldoril D30;Aldoril D50;Apo-Methyldopa;Bayer 1440 L;Baypresol;Becanta;Dopamet;Dopamethyperpax;Dopatec;Dopegyt;Grospisk;Hyperpax;Hypolag;Medomet;Medopa;Medopal;Medopren;Methoplain;Novomedopa;Nu-Medopa;Presinol;Presolisin;Sedometil;Sembrina;

Alpha medopa;Alphamethyldopa;AMD;L-Methyl Dopa;Methyldopa anhydrous;Methyldopate;Methyldopate HCL;Mk. b51;

An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent. [PubChem]

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• Watson laboratories inc

Synthesis Reference

Not Available

General Reference

Mah GT, Tejani AM, Musini VM: Methyldopa for primary hypertension. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD003893. Pubmed McCoy S, Baldwin K: Pharmacotherapeutic options for the treatment of preeclampsia. Am J Health Syst Pharm. 2009 Feb 15;66(4):337-44. Pubmed Sica DA: Centrally acting antihypertensive agents: an update. J Clin Hypertens (Greenwich). 2007 May;9(5):399-405. Pubmed van Zwieten PA: Development and trends in the drug treatment of essential hypertension. J Hypertens Suppl. 1992 Dec;10(7):S1-12. Pubmed Rosenthal T, Oparil S: The effect of antihypertensive drugs on the fetus. J Hum Hypertens. 2002 May;16(5):293-8. Pubmed van Zwieten PA, Timmermans PB: Pharmacology and characterization of central alpha-adrenoceptors involved in the effect of centrally acting antihypertensive drugs. Chest. 1983 Feb;83(2 Suppl):340-3. Pubmed van Zwieten PA: Pharmacology of centrally acting hypotensive drugs. Br J Clin Pharmacol. 1980;10 Suppl 1:13S-20S. Pubmed

Form	Route	Strength
Tablet	Oral

Unit description	Cost	Unit
Aldoclor 250-250 mg tablet	0.67 USD	tablet
Methyldopa 500 mg tablet	0.67 USD	tablet
Methyldopa 250 mg tablet	0.39 USD	tablet
Apo-Methyldopa 500 mg Tablet	0.27 USD	tablet
Methyldopate 250 mg/5 ml vial	0.24 USD	ml
Apo-Methyldopa 250 mg Tablet	0.15 USD	tablet
Apo-Methyldopa 125 mg Tablet	0.1 USD	tablet

Type	small molecule

Classes

Phenols and Derivatives Amino Acids Amphetamines Catecholamines and Derivatives

Substructures

Hydroxy Compounds Phenols and Derivatives Acetates Aliphatic and Aryl Amines Benzene and Derivatives Carboxylic Acids and Derivatives Catechols Phenethylamines Aromatic compounds Amino Acids Phenyl Esters Amphetamines Catecholamines and Derivatives

ANTIHYPERTENSIVES 降血压;

Indication	For use in the treatment of hypertension.
Pharmacodynamics	Methyldopa is an aromatic-amino-acid decarboxylase inhibitor in animals and in man. Only methyldopa, the L-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.
Mechanism of action	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.
Absorption	Absorption from the gastrointestinal tract is variable but averages approximately 50%.
Volume of distribution	Not Available
Protein binding	Low (less than 20%).
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: α-methyldopa mono-O-sulfate; 3-0-methyl-α-methyldopa; 3,4-dihydroxyphenylacetone; α-methyldopamine; 3-0-methyl-α-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.
Clearance	Renal cl=130 mL/min [healthy]
Toxicity	The oral LD50 of methyldopa is greater than 1.5 g/kg in both the mouse and the rat. Symptoms of overdose include bloating, constipation, diarrhea, dizziness, extreme drowsiness, gas, light-headedness, nausea, severely low blood pressure, slow heartbeat, vomiting, and weakness.
Affected organisms	Humans and other mammals
Pathways	Not Available

Properties
State	solid
Melting point	300 oC
Experimental Properties	Property Value Source water solubility 1000 mg/L PhysProp logP -1.7 PhysProp
Predicted Properties	Property Value Source water solubility 2.26e+00 g/l ALOGPS logP -2.02 ALOGPS logP -1.50 ChemAxon Molconvert logS -1.97 ALOGPS pKa 9.14 ChemAxon Molconvert hydrogen acceptor count 5 ChemAxon Molconvert hydrogen donor count 4 ChemAxon Molconvert polar surface area 103.78 ChemAxon Molconvert rotatable bond count 3 ChemAxon Molconvert refractivity 53.79 ChemAxon Molconvert polarizability 20.79 ChemAxon Molconvert

Drug	Interaction
Carteolol	Possible hypertensive crisis
Dobutamine	Increased arterial pressure
Dopamine	Increased arterial pressure
Entacapone	Entacapone may increase the effect and toxicity of the sympathomimetic, methyldopa.
Ephedra	Increased arterial pressure
Ephedrine	Increased arterial pressure
Epinephrine	Increased arterial pressure
Fenoterol	Increased arterial pressure
Haloperidol	Methyldopa increases haloperidol effect or risk of psychosis
Iron	Iron decreases the absorption of dopa derivatives
Iron Dextran	Iron decreases the absorption of dopa derivatives
Isoproterenol	Increased arterial pressure
Levodopa	Methyldopa increases the effect and toxicity of levodopa
Lithium	Methyldopa may increase the adverse effects of lithium without affecting lithium serum levels. Monitor for signs and symptoms of lithium toxicity during concomitant therapy.
Mephentermine	Increased arterial pressure
Metaraminol	Increased arterial pressure
Methoxamine	Increased arterial pressure
Nadolol	Possible hypertensive crisis
Norepinephrine	Increased arterial pressure
Orciprenaline	Increased arterial pressure
Oxprenolol	Possible hypertensive crisis
Penbutolol	Possible hypertensive crisis
Phenylephrine	Increased arterial pressure
Phenylpropanolamine	Increased arterial pressure
Pindolol	Possible hypertensive crisis
Pirbuterol	Increased arterial pressure
Procaterol	Increased arterial pressure
Propranolol	Possible hypertensive crisis
Pseudoephedrine	Increased arterial pressure
Salbutamol	Increased arterial pressure
Sotalol	Possible hypertensive crisis
Terbutaline	Increased arterial pressure
Timolol	Possible hypertensive crisis
Tranylcypromine	The MAO inhibitor, Tranylcypromine, may increase the adverse effects of Methyldopa. Concomitant therapy is contraindicated.

• Avoid alcohol.
• Avoid natural licorice.
• Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a multivitamin.
• May take Vitamin D.
• No iron, zinc or fluoride within 2 hours of taking this medication.
• Take without regard to meals.