Methyldopa

Identification

Summary

Methyldopa is a centrally-acting alpha-2 adrenergic agonist used to manage hypertension alone or in combination with hydrochlorothiazide, and to treat hypertensive crises.

Generic Name
Methyldopa
DrugBank Accession Number
DB00968
Background

Methyldopa, or α-methyldopa, is a centrally acting sympatholytic agent and an antihypertensive agent.4 It is an analog of DOPA (3,4‐hydroxyphenylanine), and it is a prodrug, meaning that the drug requires biotransformation to an active metabolite for therapeutic effects. Methyldopa works by binding to alpha(α)-2 adrenergic receptors as an agonist, leading to the inhibition of adrenergic neuronal outflow and reduction of vasoconstrictor adrenergic signals.1 Methyldopa exists in two isomers D-α-methyldopa and L-α-methyldopa, which is the active form.7

First introduced in 1960 as an antihypertensive agent, methyldopa was considered to be useful in certain patient populations, such as pregnant women and patients with renal insufficiency. Since then, methyldopa was largely replaced by newer, better-tolerated antihypertensive agents;4 however, it is still used as monotherapy 11 or in combination with hydrochlorothiazide.12 Methyldopa is also available as intravenous injection, which is used to manage hypertension when oral therapy is unfeasible and to treat hypertensive crisis.13

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 211.2145
Monoisotopic: 211.084457909
Chemical Formula
C10H13NO4
Synonyms
  • (S)-(-)-alpha-Methyldopa
  • 3-Hydroxy-alpha-methyl-L-tyrosine
  • Alpha medopa
  • alpha-Methyl dopa
  • alpha-methyl-L-dopa
  • Alphamethyldopa
  • AMD
  • Anhydrous methyldopa
  • L-alpha-Methyldopa
  • L-Methyl Dopa
  • Methyl dopa
  • Methyldopa
  • Methyldopa anhydrous
  • metildopa
  • α-Methyl dopa
  • α-methyl-L-dopa
External IDs
  • Bayer 1440L
  • J9.247I

Pharmacology

Indication

Methyldopa is indicated for the management of hypertension as monotherapy 11 or in combination with hydrochlorothiazide.12 Methyldopa injection is used to manage hypertensive crises.13

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Antihypertensive effects of methyldopa are mostly mediated by its pharmacologically active metabolite, alpha-methylnorepinephrine, which works as an agonist at central inhibitory alpha-adrenergic receptors.11 Stimulation of alpha-adrenergic receptors leads to decreased peripheral sympathetic tone and reduced arterial pressure.3 Methyldopa causes a net reduction in the tissue concentration of serotonin, dopamine, norepinephrine, and epinephrine. Overall, methyldopa lowers both standing blood pressure and especially supine blood pressure, with infrequent symptomatic postural hypotension. Methyldopa also reduces plasma renin activity but has negligible effects on glomerular filtration rate, renal blood flow, or filtration fraction. It also has no direct effect on cardiac function but in some patients, a slowed heart rate may occur.11

Following oral administration, blood-pressure-lowering effects are observed within 12 to 24 hours in most patients, and a maximum reduction in blood pressure occurs in 4 to 6 hours. Blood pressure returns to pre-treatment levels within 24 to 48 hours following drug discontinuation.11 Following intravenous administration, the blood-pressure-lowering effects of methyldopa last for about 10 to 16 hours.4

Mechanism of action

The exact mechanism of methyldopa is not fully elucidated; however, the main mechanisms of methyldopa involve its actions on alpha-adrenergic receptor and the aromatic L-amino acid decarboxylase enzyme, to a lesser extent. The sympathetic outflow is regulated by alpha (α)-2 adrenergic receptors and imidazoline receptors expressed on adrenergic neurons within the rostral ventrolateral medulla.2 Methyldopa is metabolized to α‐methylnorepinephrine via dopamine beta-hydroxylase activity and, consequently, alpha-methylepinephrine via phenylethanolamine-N-methyltransferase activity.9,8,10 Mediating the therapeutic effects of methyldopa, α‐methylnorepinephrine and α-methylepinephrine active metabolites are agonists at presynaptic alpha-2 adrenergic receptors in the brainstem. Stimulating alpha-2 adrenergic receptors results in the inhibition of adrenergic neuronal outflow and attenuation of norepinephrine release in the brainstem. Consequently, the output of vasoconstrictor adrenergic signals to the peripheral sympathetic nervous system is reduced, leading to a reduction in blood pressure.1

The L-isomer of alpha-methyldopa also reduces blood pressure by inhibiting aromatic L-amino acid decarboxylase, also known as DOPA decarboxylase, which is an enzyme responsible for the syntheses of dopamine and serotonin.11 Inhibiting this enzyme leads to depletion of biogenic amines such as norepinephrine. However, inhibition of aromatic L-amino acid decarboxylase plays a minimal role in the blood-pressure‐lowering effect of methyldopa.2,3

TargetActionsOrganism
AAlpha-2A adrenergic receptor
agonist
Humans
AAromatic-L-amino-acid decarboxylase
inhibitor
Humans
Absorption

Methyldopa is incompletely absorbed from the gastrointestinal tract following oral administration.5 In healthy individuals, the inactive D-isomer is less readily absorbed than the active L-isomer.7 The mean bioavailability of methyldopa is 25%, ranging from eight to 62%.5 Following oral administration, about 50% of the dose is absorbed and Tmax is about three to six hours.6,4

Volume of distribution

The apparent volume of distribution ranges between 0.19 and 0.32L/kg and the total volume of distribution ranges from 0.41 to 0.72L/kg. Since methyldopa is lipid-soluble 4, it crosses the placental barrier, appears in cord blood, and appears in breast milk.11

Protein binding

Methyldopa is less than 15% bound to plasma proteins and its primary metabolite, O-sulfate metabolite, is about 50% protein bound.5 Following intravenous administration, approximately 17% of the dose in normal subjects were circulating in the plasma as free methyldopa.13

Metabolism

Two isomers of methyldopa undergo different metabolic pathways.7 L-α-methyldopa is biotransformed to its pharmacologically active metabolite, alpha-methylnorepinephrine. Methyldopa is extensively metabolized in the liver to form the main circulating metabolite in the plasma, alpha (α)-methyldopa mono-O-sulfate. Its other metabolites also include 3-O-methyl-α-methyldopa; 3,4-dihydroxyphenylacetone; α-methyldopamine; and 3-O-methyl-α-methyldopamine. These metabolites are further conjugated in the liver to form sulfate conjugates.11 After intravenous administration, the most prominent metabolites are alpha-methyldopamine and the glucuronide of dihydroxyphenylacetone, along with other uncharacterized metabolites.5

D-α-methyldopa, which is the inactive isomer of methyldopa, is also metabolized to 3-O-methyl-α-methyldopa and 3,4-dihydroxyphenylacetone to a minimal extent; however, there are no amines (α-methyldopamine and 3-O-methyl-α-methyldopamine) formed.7

Hover over products below to view reaction partners

Route of elimination

Approximately 70% of absorbed methyldopa is excreted in the urine as unchanged parent drug (24%) and α-methyldopa mono-O-sulfate (64%),6,11 with variability.3-O-methyl-α-methyldopa accounted for about 4% of urinary excretion products. Other metabolites like 3,4-dihydroxyphenylacetone, α-methyldopamine, and 3-O-methyl-α-methyldopamine are also excreted in urine.6

Unabsorbed drug is excreted in feces as the unchanged parent compound.4 After oral doses, excretion is essentially complete in 36 hours.12

Due to attenuated excretion in patients with renal failure, accumulation of the drug and its metabolites may occur,4 possibly leading to more profound and prolonged hypotensive effects in these patients.5

Half-life

The plasma half-life of methyldopa is 105 minutes.11 Following intravenous injection, the plasma half-life of methyldopa ranges from 90 to 127 minutes.13

Clearance

The renal clearance is about 130 mL/min in normal subjects and is decreased in patients with renal insufficiency.11

Adverse Effects
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Toxicity

The lowest published toxic dose via oral route is 44 gm/kg/3Y (intermittent) in a female. Oral LD50 is 5000 mg/kg in rats and 5300 mg/kg in mice. Intraperitoneal LD50 is 300 mg/kg in rats and 150 mg/kg in mice.14

Acute overdosage is characterized by acute hypotension and other presentations attributed to the brain and gastrointestinal dysfunction, such as excessive sedation, weakness, bradycardia, dizziness, light-headedness, constipation, distention, flatus, diarrhea, nausea, and vomiting. Symptomatic and supportive measures should be initiated in the event of methyldopa overdose. Overdosage following recent oral ingestion can be managed by gastric lavage or emesis, as well as infusions to limit further drug absorption. Cardiac rate and output, blood volume, electrolyte balance, paralytic ileus, urinary function and cerebral activity should be closely monitored. The use of sympathomimetic drugs such as levarterenol, epinephrine, and metaraminol bitartrate, or dialysis may be considered.11

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirMethyldopa may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcebutololThe therapeutic efficacy of Methyldopa can be decreased when used in combination with Acebutolol.
AceclofenacThe therapeutic efficacy of Methyldopa can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Methyldopa can be decreased when used in combination with Acemetacin.
AcetaminophenAcetaminophen may decrease the excretion rate of Methyldopa which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Methyldopa which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Methyldopa which could result in a higher serum level.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Methyldopa is combined with Acipimox.
AclidiniumMethyldopa may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineMethyldopa may decrease the excretion rate of Acrivastine which could result in a higher serum level.
Interactions
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Food Interactions
  • Take with or without food. Drug pharmacokinetics is unaffected.

Products

Products
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Product Ingredients
IngredientUNIICASInChI Key
Methyldopa hydrochloride7PX435DN5A2508-79-4QSRVZCCJDKYRRF-YDALLXLXSA-N
Methyldopa sesquihydrate56LH93261Y41372-08-1YKFCISHFRZHKHY-NGQGLHOPSA-N
Product Images
International/Other Brands
Aldomet / Aldometil / Aldomin / Dopamet / Hypolag / Medomet / Medopren / Novomedopa / Nu-Medopa
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Aldomet Ester HCl InjLiquid250 mg / 5 mLIntravenousMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1963-12-312002-07-29Canada flag
Aldomet Tab 125mgTablet125 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1971-12-311998-08-14Canada flag
Aldomet Tab 250mgTablet250 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1963-12-312004-11-12Canada flag
Aldomet Tab 500mgTablet500 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1971-12-311998-08-14Canada flag
Dopamet Tab 125mgTablet125 mgOralIcn Pharmaceuticals1976-12-312005-04-26Canada flag
Dopamet Tab 250mgTablet250 mgOralIcn Pharmaceuticals1972-12-312005-04-26Canada flag
Dopamet Tab 500mgTablet500 mgOralIcn Pharmaceuticals1976-12-312005-04-26Canada flag
Medimet 250tabTablet250 mgOralMedic Laboratory LtÉe1976-12-311996-09-09Canada flag
MethyldopaTablet500 mgOralAa Pharma Inc1978-12-31Not applicableCanada flag
MethyldopaTablet250 mgOralAa Pharma Inc1976-12-31Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MethyldopaTablet, film coated500 mg/1OralAvera McKennan Hospital2016-04-182017-05-24US flag
MethyldopaTablet, film coated500 mg/1OralTeva Pharmaceuticals USA, Inc.2009-04-282018-02-28US flag0093 293220180814 13942 1z117lk
MethyldopaTablet250 mg/1OralMylan Institutional Inc.1998-09-012020-01-31US flag
MethyldopaTablet, film coated500 mg/1OralIVAX Pharmaceuticals, Inc.1986-02-201993-07-31US flag
MethyldopaTablet, film coated250 mg/1OralRebel Distributors1984-02-20Not applicableUS flag
MethyldopaTablet, film coated125 mg/1OralAccord Healthcare Inc.2012-06-272012-06-27US flag
MethyldopaTablet, film coated250 mg/1OralCarilion Materials Management2012-07-24Not applicableUS flag
MethyldopaTablet, film coated250 mg/1OralRebel Distributors2009-02-23Not applicableUS flag42254 035120210427 24843 8w56e6
MethyldopaTablet, film coated250 mg/1OralTeva Pharmaceuticals USA, Inc.2009-02-232018-02-28US flag0093 293120180814 13942 1rt80a7
MethyldopaTablet, film coated500 mg/1OralAccord Healthcare Inc.2012-07-242022-08-31US flag16729 0031 01 nlmimage10 6440b275
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
AldorilMethyldopa sesquihydrate (500 mg/1) + Hydrochlorothiazide (30 mg/1)Tablet, film coatedOralMerck Sharp & Dohme Limited1962-12-202006-03-31US flag
AldorilMethyldopa sesquihydrate (250 mg/1) + Hydrochlorothiazide (25 mg/1)Tablet, film coatedOralMerck Sharp & Dohme Limited1962-12-202006-03-31US flag
AldorilMethyldopa sesquihydrate (500 mg/1) + Hydrochlorothiazide (50 mg/1)Tablet, film coatedOralMerck Sharp & Dohme Limited1962-12-202006-03-31US flag
AldorilMethyldopa sesquihydrate (250 mg/1) + Hydrochlorothiazide (15 mg/1)Tablet, film coatedOralMerck Sharp & Dohme Limited1962-12-202006-03-31US flag
Aldoril 15 TabMethyldopa (250 mg) + Hydrochlorothiazide (15 mg)TabletOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1967-12-311998-08-14Canada flag
Aldoril 25 TabMethyldopa (250 mg) + Hydrochlorothiazide (25 mg)TabletOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1963-12-311999-03-02Canada flag
Apo Methazide 15Methyldopa (250 mg) + Hydrochlorothiazide (15 mg)TabletOralApotex Corporation1984-12-312019-05-04Canada flag
Apo Methazide 25Methyldopa (250 mg) + Hydrochlorothiazide (25 mg)TabletOralApotex Corporation1984-12-312019-05-04Canada flag
Methyldopa and HydrochlorothiazideMethyldopa sesquihydrate (250 mg/1) + Hydrochlorothiazide (15 mg/1)TabletOralMylan Pharmaceuticals Inc.1986-01-23Not applicableUS flag
Methyldopa and HydrochlorothiazideMethyldopa sesquihydrate (250 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralPhysicians Total Care, Inc.1986-02-152012-06-30US flag

Categories

ATC Codes
C02AB01 — Methyldopa (levorotatory)
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylpropanoic acids. These are compounds with a structure containing a benzene ring conjugated to a propanoic acid.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Phenylpropanoic acids
Sub Class
Not Available
Direct Parent
Phenylpropanoic acids
Alternative Parents
D-alpha-amino acids / Amphetamines and derivatives / Phenylpropanes / Catechols / Aralkylamines / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids
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Substituents
1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / 3-phenylpropanoic-acid / Alpha-amino acid / Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Amphetamine or derivatives / Aralkylamine
show 20 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
non-proteinogenic L-alpha-amino acid, L-tyrosine derivative (CHEBI:61058)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
M4R0H12F6M
CAS number
555-30-6
InChI Key
CJCSPKMFHVPWAR-JTQLQIEISA-N
InChI
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
IUPAC Name
(2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid
SMILES
C[C@](N)(CC1=CC=C(O)C(O)=C1)C(O)=O

References

Synthesis Reference
US2868818
General References
  1. Mah GT, Tejani AM, Musini VM: Methyldopa for primary hypertension. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD003893. doi: 10.1002/14651858.CD003893.pub3. [Article]
  2. Sica DA: Centrally acting antihypertensive agents: an update. J Clin Hypertens (Greenwich). 2007 May;9(5):399-405. [Article]
  3. van Zwieten PA: Pharmacology of centrally acting hypotensive drugs. Br J Clin Pharmacol. 1980;10 Suppl 1:13S-20S. [Article]
  4. Gupta M, Al Khalili Y: Methyldopa . [Article]
  5. Myhre E, Rugstad HE, Hansen T: Clinical pharmacokinetics of methyldopa. Clin Pharmacokinet. 1982 May-Jun;7(3):221-33. doi: 10.2165/00003088-198207030-00003. [Article]
  6. BUHS RP, BECK JL, SPETH OC, SMITH JL, TRENNER NR, CANNON PJ, LARAGH JH: THE METABOLISM OF METHYLDOPA IN HYPERTENSIVE HUMAN SUBJECTS. J Pharmacol Exp Ther. 1964 Feb;143:205-14. [Article]
  7. Au WY, Dring LG, Grahame-Smith DG, Isaac P, Williams RT: The metabolism of 14 C-labelled -methyldopa in normal and hypertensive human subjects. Biochem J. 1972 Aug;129(1):1-10. doi: 10.1042/bj1290001. [Article]
  8. Tung CS, Goldberg MR, Hollister AS, Oates JA, Robertson D: Central and peripheral cardiovascular effects of alpha-methylepinephrine. J Pharmacol Exp Ther. 1983 Nov;227(2):484-90. [Article]
  9. Goldberg MR, Gerkens JF, Oates JA, Robertson D: alpha-Methylepinephrine, a methyldopa metabolite that binds to alpha-receptors in rat brain. Eur J Pharmacol. 1981 Jan 5;69(1):95-9. doi: 10.1016/0014-2999(81)90606-3. [Article]
  10. Robertson D, Tung CS, Goldberg MR, Hollister AS, Gerkens JF, Oates JA: Antihypertensive metabolites of alpha-methyldopa. Hypertension. 1984 Sep-Oct;6(5 Pt 2):II45-50. doi: 10.1161/01.hyp.6.5_pt_2.ii45. [Article]
  11. DailyMed Label: METHYLDOPA oral tablet, film coated [Link]
  12. DailyMed Label: METHYLDOPA AND HYDROCHLOROTHIAZIDE oral tablet [Link]
  13. DailyMed Label: Methyldopate Intravenous Injection [Link]
  14. Cayman Chemical: Methyldopa Safety Data Sheet [Link]
Human Metabolome Database
HMDB0011754
KEGG Drug
D08205
KEGG Compound
C07194
PubChem Compound
38853
PubChem Substance
46508535
ChemSpider
35562
BindingDB
48449
RxNav
1545996
ChEBI
61058
ChEMBL
CHEMBL459
ZINC
ZINC000000020255
Therapeutic Targets Database
DAP000226
PharmGKB
PA450453
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Methyldopa
FDA label
Download (155 KB)
MSDS
Download (53.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentHypertension in Pregnancy / Prophylaxis of preeclampsia1
4Enrolling by InvitationTreatmentPostpartum Hypertension1
4RecruitingPreventionPregnancy Induced Hypertension (PIH) / Prophylaxis of preeclampsia1
4Unknown StatusDiagnosticProphylaxis of preeclampsia1
4Unknown StatusTreatmentDiabetes / Hypertensive Diseases1
4Unknown StatusTreatmentProphylaxis of preeclampsia1
3CompletedTreatmentAutonomic Nervous System Diseases / Dopamine Beta Hydroxylase Deficiency / Orthostatic Hypotension / Orthostatic Intolerance1
2CompletedTreatmentPregnant Women With Mild Preeclampsia1
2WithdrawnPreventionType 1 Diabetes Mellitus1
1CompletedNot AvailableMyalgic Encephalomyelitis (ME) / Orthostatic Intolerance / Postural Tachycardia Syndrome1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Advanced Pharmaceutical Services Inc.
  • American Regent
  • A-S Medication Solutions LLC
  • Caremark LLC
  • Central Texas Community Health Centers
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Emcure Pharmaceuticals Ltd.
  • Endo Pharmaceuticals Inc.
  • H and H Laboratories
  • Heartland Repack Services LLC
  • Hospira Inc.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Luitpold Pharmaceuticals Inc.
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
Tablet, coatedOral
TabletOral283 mg
LiquidIntravenous250 mg / 5 mL
Tablet, film coatedOral
Tablet, film coatedOral
Capsule
TabletOral125 mg
TabletOral250 mg/1
TabletOral500 mg/1
Tablet, film coatedOral125 mg/1
Tablet, film coatedOral250 mg/1
Tablet, film coatedOral500 mg/1
TabletOral
Injection, solutionIntravenous50 mg/1mL
TabletOral500 mg
TabletOral250 mg
TabletOral
Tablet, film coatedOral500 mg
Tablet, delayed releaseOral250 mg
Tablet, film coatedOral250 mg
Tablet, film coatedOral125 mg
Prices
Unit descriptionCostUnit
Aldoclor 250-250 mg tablet0.67USD tablet
Methyldopa 500 mg tablet0.67USD tablet
Methyldopa 250 mg tablet0.39USD tablet
Apo-Methyldopa 500 mg Tablet0.27USD tablet
Methyldopate 250 mg/5 ml vial0.24USD ml
Apo-Methyldopa 250 mg Tablet0.15USD tablet
Apo-Methyldopa 125 mg Tablet0.1USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)>300https://www.fishersci.ca/store/msds?partNumber=AAH5670403&productDescription=3-4-dihydroxy-alpha-methyl-l-phenylalanine-sesquihydrate-99&language=en&countryCode=CA
water solubility1E+004 mg/L (at 25 °C)MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility2.26 mg/mLALOGPS
logP-2ALOGPS
logP-1.4ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)1.73ChemAxon
pKa (Strongest Basic)9.85ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area103.78 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity53.79 m3·mol-1ChemAxon
Polarizability20.73 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9374
Blood Brain Barrier-0.9276
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.6066
P-glycoprotein inhibitor INon-inhibitor0.9852
P-glycoprotein inhibitor IINon-inhibitor0.9895
Renal organic cation transporterNon-inhibitor0.9357
CYP450 2C9 substrateNon-substrate0.7757
CYP450 2D6 substrateNon-substrate0.8
CYP450 3A4 substrateNon-substrate0.6053
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9369
CYP450 2D6 inhibitorNon-inhibitor0.9491
CYP450 2C19 inhibitorNon-inhibitor0.9233
CYP450 3A4 inhibitorNon-inhibitor0.864
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9551
Ames testNon AMES toxic0.8185
CarcinogenicityNon-carcinogens0.8997
BiodegradationNot ready biodegradable0.8077
Rat acute toxicity1.6281 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9939
hERG inhibition (predictor II)Non-inhibitor0.9629
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-001i-0690000000-f54d986a8144f4a79b82
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0g5i-2900000000-2d1c0ec9ad93e208b620

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Sica DA: Centrally acting antihypertensive agents: an update. J Clin Hypertens (Greenwich). 2007 May;9(5):399-405. [Article]
  4. Kawasaki H: [Centrally acting sympathetic inhibitors for therapy of patients with hypertension]. Nihon Rinsho. 1997 Aug;55(8):2081-5. [Article]
  5. Head GA: Central imidazoline- and alpha 2-receptors involved in the cardiovascular actions of centrally acting antihypertensive agents. Ann N Y Acad Sci. 1999 Jun 21;881:279-86. [Article]
  6. van Zwieten PA: New central mediators as targets of centrally acting antihypertensive drugs. Clin Exp Hypertens. 1996 Apr-May;18(3-4):291-303. [Article]
  7. van Zwieten PA: Development and trends in the drug treatment of essential hypertension. J Hypertens Suppl. 1992 Dec;10(7):S1-12. [Article]
  8. Velliquette RA, Ernsberger P: Contrasting metabolic effects of antihypertensive agents. J Pharmacol Exp Ther. 2003 Dec;307(3):1104-11. Epub 2003 Oct 13. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Pyridoxal phosphate binding
Specific Function
Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Gene Name
DDC
Uniprot ID
P20711
Uniprot Name
Aromatic-L-amino-acid decarboxylase
Molecular Weight
53925.815 Da
References
  1. SOURKES TL: Inhibition of dihydroxy-phenylalanine decarboxylase by derivatives of phenylalanine. Arch Biochem Biophys. 1954 Aug;51(2):444-56. [Article]
  2. Campbell NR, Sundaram RS, Werness PG, Van Loon J, Weinshilboum RM: Sulfate and methyldopa metabolism: metabolite patterns and platelet phenol sulfotransferase activity. Clin Pharmacol Ther. 1985 Mar;37(3):308-15. doi: 10.1038/clpt.1985.45. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
O-methyltransferase activity
Specific Function
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOP...
Gene Name
COMT
Uniprot ID
P21964
Uniprot Name
Catechol O-methyltransferase
Molecular Weight
30036.77 Da
References
  1. Alazizi A, Liu MY, Williams FE, Kurogi K, Sakakibara Y, Suiko M, Liu MC: Identification, characterization, and ontogenic study of a catechol O-methyltransferase from zebrafish. Aquat Toxicol. 2011 Mar;102(1-2):18-23. doi: 10.1016/j.aquatox.2010.12.016. Epub 2010 Dec 29. [Article]
  2. Ameyaw MM, Syvanen AC, Ulmanen I, Ofori-Adjei D, McLeod HL: Pharmacogenetics of catechol-O-methyltransferase: frequency of low activity allele in a Ghanaian population. Hum Mutat. 2000 Nov;16(5):445-6. [Article]
  3. Campbell NR, Sundaram RS, Werness PG, Van Loon J, Weinshilboum RM: Sulfate and methyldopa metabolism: metabolite patterns and platelet phenol sulfotransferase activity. Clin Pharmacol Ther. 1985 Mar;37(3):308-15. doi: 10.1038/clpt.1985.45. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Pyridoxal phosphate binding
Specific Function
Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Gene Name
DDC
Uniprot ID
P20711
Uniprot Name
Aromatic-L-amino-acid decarboxylase
Molecular Weight
53925.815 Da
References
  1. Campbell NR, Sundaram RS, Werness PG, Van Loon J, Weinshilboum RM: Sulfate and methyldopa metabolism: metabolite patterns and platelet phenol sulfotransferase activity. Clin Pharmacol Ther. 1985 Mar;37(3):308-15. doi: 10.1038/clpt.1985.45. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sulfotransferase activity
Specific Function
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfonation of steroids and bile acids in the liver and adrenal glands.

Components:
References
  1. Campbell NR, Sundaram RS, Werness PG, Van Loon J, Weinshilboum RM: Sulfate and methyldopa metabolism: metabolite patterns and platelet phenol sulfotransferase activity. Clin Pharmacol Ther. 1985 Mar;37(3):308-15. doi: 10.1038/clpt.1985.45. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
L-ascorbic acid binding
Specific Function
Conversion of dopamine to noradrenaline.
Gene Name
DBH
Uniprot ID
P09172
Uniprot Name
Dopamine beta-hydroxylase
Molecular Weight
69064.45 Da
References
  1. Robertson D, Tung CS, Goldberg MR, Hollister AS, Gerkens JF, Oates JA: Antihypertensive metabolites of alpha-methyldopa. Hypertension. 1984 Sep-Oct;6(5 Pt 2):II45-50. doi: 10.1161/01.hyp.6.5_pt_2.ii45. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Phenylethanolamine n-methyltransferase activity
Specific Function
Converts noradrenaline to adrenaline.
Gene Name
PNMT
Uniprot ID
P11086
Uniprot Name
Phenylethanolamine N-methyltransferase
Molecular Weight
30854.745 Da
References
  1. Robertson D, Tung CS, Goldberg MR, Hollister AS, Gerkens JF, Oates JA: Antihypertensive metabolites of alpha-methyldopa. Hypertension. 1984 Sep-Oct;6(5 Pt 2):II45-50. doi: 10.1161/01.hyp.6.5_pt_2.ii45. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Hubbard AK, Lohr CL, Hastings K, Clarke JB, Gandolfi AJ: Immunogenicity studies of a synthetic antigen of alpha methyl dopa. Immunopharmacol Immunotoxicol. 1993 Nov;15(5):621-37. doi: 10.3109/08923979309019734. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Han HK, Rhie JK, Oh DM, Saito G, Hsu CP, Stewart BH, Amidon GL: CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs. J Pharm Sci. 1999 Mar;88(3):347-50. [Article]

Drug created on June 13, 2005 13:24 / Updated on July 29, 2021 06:27