L methyldopa n-acetyl hóa tách đối quang bằng phenylethylamin hbr năm 2024

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 NameMethyldopaDrugBank Accession NumberDB00968Background

Methyldopa, or α-methyldopa, is a centrally acting sympatholytic agent and an antihypertensive agent. 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. Methyldopa exists in two isomers D-α-methyldopa and L-α-methyldopa, which is the active form.

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; however, it is still used as monotherapy or in combination with hydrochlorothiazide. Methyldopa is also available as intravenous injection, which is used to manage hypertension when oral therapy is unfeasible and to treat hypertensive crisis.

TypeSmall MoleculeGroupsApprovedStructure

WeightAverage: 211.2145 Monoisotopic: 211.084457909 Chemical FormulaC10H13NO4Synonyms

• [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 Indication

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

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Associated ConditionsContraindications & Blackbox WarningsPharmacodynamics

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. Stimulation of alpha-adrenergic receptors leads to decreased peripheral sympathetic tone and reduced arterial pressure. 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.

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. Following intravenous administration, the blood-pressure-lowering effects of methyldopa last for about 10 to 16 hours.

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. Methyldopa is metabolized to α‐methylnorepinephrine via dopamine beta-hydroxylase activity and, consequently, alpha-methylepinephrine via phenylethanolamine-N-methyltransferase activity.,, 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.

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. 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.,

TargetActionsOrganismA

inhibitor

HumansA

agonist

HumansAbsorption

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

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 , it crosses the placental barrier, appears in cord blood, and appears in breast milk.

Protein binding

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

Metabolism

Two isomers of methyldopa undergo different metabolic pathways. 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. After intravenous administration, the most prominent metabolites are alpha-methyldopamine and the glucuronide of dihydroxyphenylacetone, along with other uncharacterized metabolites.

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.

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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%],, 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.

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

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

Half-life

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

Clearance

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

Adverse EffectsToxicity

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.

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.

PathwaysNot AvailablePharmacogenomic Effects/ADRs Not AvailableDrug 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

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AbacavirMethyldopa may decrease the excretion rate of Abacavir which could result in a higher serum level.AbaloparatideThe risk or severity of adverse effects can be increased when Methyldopa is combined with Abaloparatide.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.Food Interactions

• Take with or without food. Drug pharmacokinetics is unaffected.

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Product Ingredients IngredientUNIICASInChI KeyMethyldopa hydrochloride7PX435DN5A2508-79-4QSRVZCCJDKYRRF-YDALLXLXSA-NMethyldopa sesquihydrate56LH93261Y41372-08-1YKFCISHFRZHKHY-NGQGLHOPSA-NProduct ImagesInternational/Other BrandsAldomet / Aldometil / Aldomin / Dopamet / Hypolag / Medomet / Medopren / Novomedopa / Nu-MedopaBrand Name Prescription ProductsGeneric Prescription ProductsMixture ProductsATC CodesC02AB01 — Methyldopa [levorotatory]

• C02AB — Methyldopa
• C02A — ANTIADRENERGIC AGENTS, CENTRALLY ACTING
• C02 — ANTIHYPERTENSIVES
• C — CARDIOVASCULAR SYSTEM Drug Categories
• Adrenergic Agents
• Adrenergic Agonists
• Adrenergic alpha-2 Receptor Agonists
• Adrenergic alpha-Agonists
• Agents Causing Muscle Toxicity
• Amines
• Amino Acids
• Amino Acids, Aromatic
• Amino Acids, Cyclic
• Amino Acids, Peptides, and Proteins
• Antiadrenergic Agents, Centrally Acting
• Antihypertensive Agents
• Antihypertensive Agents Indicated for Hypertension
• Aromatic L-amino Acid Decarboxylase Inhibitors
• Autonomic Agents
• Benzene Derivatives
• Bradycardia-Causing Agents
• Cardiovascular Agents
• Catecholamines
• Catechols
• Central alpha-2 Adrenergic Agonist
• Central Alpha-agonists
• COMT Substrates
• Dihydroxyphenylalanine
• Drugs that are Mainly Renally Excreted
• Enzyme Inhibitors
• Hypotensive Agents
• Neurotransmitter Agents
• Peripheral Nervous System Agents
• Phenols
• Sympatholytics

Chemical TaxonomyProvided by ClassyfireDescriptionThis 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.KingdomOrganic compoundsSuper ClassPhenylpropanoids and polyketidesClassPhenylpropanoic acidsSub ClassNot AvailableDirect ParentPhenylpropanoic acidsAlternative ParentsD-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 show 5 moreSubstituents1-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 moreMolecular FrameworkAromatic homomonocyclic compoundsExternal Descriptorsnon-proteinogenic L-alpha-amino acid, L-tyrosine derivative [CHEBI:61058] Affected organisms

• Humans and other mammals UNIIM4R0H12F6MCAS number555-30-6InChI KeyCJCSPKMFHVPWAR-JTQLQIEISA-NInChI

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

Synthesis ReferenceGeneral 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] External LinksHuman Metabolome DatabaseHMDB0011754KEGG DrugD08205KEGG CompoundC07194PubChem Compound38853PubChem Substance46508535ChemSpider35562BindingDB48449RxNav1545996ChEBI61058ChEMBLCHEMBL459ZINCZINC000000020255Therapeutic Targets DatabaseDAP000226PharmGKBPA450453RxListRxList Drug PageDrugs.comDrugs.com Drug PagePDRhealthPDRhealth Drug PageWikipediaMethyldopaFDA labelMSDSClinical Trials 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 FormsFormRouteStrengthTabletOral500.0000 mgTablet, coatedOral250 MGTablet, coatedOral500 MGTabletOral283 mgTabletOral28300000 mgLiquidIntravenous250 mg / 5 mLTablet, film coatedOralTablet, film coatedOralCapsuleTabletOral125 mgTabletOral250 mgTabletOral250 mg/1TabletOral500 mg/1TabletOral500 mgTablet, film coatedOral125 mg/1Tablet, film coatedOral250 mg/1Tablet, film coatedOral500 mg/1TabletOralInjection, solutionIntravenous50 mg/1mLTabletOralTablet, film coatedOral500 mgTablet, delayed releaseOral250 mgTablet, film coatedOral250 mgTablet, film coatedOral125 mgPricesUnit descriptionCostUnitAldoclor 250-250 mg tablet0.67USD tabletMethyldopa 500 mg tablet0.67USD tabletMethyldopa 250 mg tablet0.39USD tabletApo-Methyldopa 500 mg Tablet0.27USD tabletMethyldopate 250 mg/5 ml vial0.24USD mlApo-Methyldopa 250 mg Tablet0.15USD tabletApo-Methyldopa 125 mg Tablet0.1USD tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

PatentsNot AvailableStateSolidExperimental PropertiesPropertyValueSourcemelting point [°C]>300//www.fishersci.ca/store/msds?partNumber=AAH5670403&productDescription=3-4-dihydroxy-alpha-methyl-l-phenylalanine-sesquihydrate-99&language=en&countryCode=CAwater solubility1E+004 mg/L [at 25 °C]MERCK INDEX [1996]Predicted PropertiesPropertyValueSourceWater Solubility2.26 mg/mLALOGPSlogP-2ALOGPSlogP-1.4ChemaxonlogS-2ALOGPSpKa [Strongest Acidic]1.73ChemaxonpKa [Strongest Basic]9.85ChemaxonPhysiological Charge0ChemaxonHydrogen Acceptor Count5ChemaxonHydrogen Donor Count4ChemaxonPolar Surface Area103.78 Å2ChemaxonRotatable Bond Count3ChemaxonRefractivity53.79 m3·mol-1ChemaxonPolarizability20.73 Å3ChemaxonNumber of Rings1ChemaxonBioavailability1ChemaxonRule of FiveYesChemaxonGhose FilterNoChemaxonVeber's RuleNoChemaxonMDDR-like RuleNoChemaxonPredicted ADMET FeaturesPropertyValueProbabilityHuman Intestinal Absorption+0.9374Blood Brain Barrier-0.9276Caco-2 permeable-0.8957P-glycoprotein substrateSubstrate0.6066P-glycoprotein inhibitor INon-inhibitor0.9852P-glycoprotein inhibitor IINon-inhibitor0.9895Renal organic cation transporterNon-inhibitor0.9357CYP450 2C9 substrateNon-substrate0.7757CYP450 2D6 substrateNon-substrate0.8CYP450 3A4 substrateNon-substrate0.6053CYP450 1A2 substrateNon-inhibitor0.9045CYP450 2C9 inhibitorNon-inhibitor0.9369CYP450 2D6 inhibitorNon-inhibitor0.9491CYP450 2C19 inhibitorNon-inhibitor0.9233CYP450 3A4 inhibitorNon-inhibitor0.864CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9551Ames testNon AMES toxic0.8185CarcinogenicityNon-carcinogens0.8997BiodegradationNot ready biodegradable0.8077Rat acute toxicity1.6281 LD50, mol/kg Not applicablehERG inhibition [predictor I]Weak inhibitor0.9939hERG inhibition [predictor II]Non-inhibitor0.9629

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. [23092397]

Mass Spec [NIST]Not AvailableSpectraSpectrumSpectrum TypeSplash KeyPredicted GC-MS Spectrum - GC-MSPredicted GC-MSGC-MS Spectrum - GC-EI-TOFGC-MSLC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSMS/MS Spectrum - , positiveLC-MS/MSPredicted MS/MS Spectrum - 10V, Positive [Annotated]Predicted LC-MS/MSPredicted MS/MS Spectrum - 10V, Negative [Annotated]Predicted LC-MS/MSPredicted MS/MS Spectrum - 20V, Positive [Annotated]Predicted LC-MS/MSPredicted MS/MS Spectrum - 20V, Negative [Annotated]Predicted LC-MS/MSPredicted MS/MS Spectrum - 40V, Negative [Annotated]Predicted LC-MS/MSPredicted MS/MS Spectrum - 40V, Positive [Annotated]Predicted LC-MS/MSPredicted 1H NMR Spectrum1D NMRNot ApplicablePredicted 13C NMR Spectrum1D NMRNot ApplicableChromatographic PropertiesCollision Cross Sections [CCS]AdductCCS Value [Å2]Source typeSource[M-H]-153.8856241

predicted

DarkChem Lite v0.1.0[M-H]-143.58476

predicted

DeepCCS 1.0 [2019][M+H]+154.1786241

predicted

DarkChem Lite v0.1.0[M+H]+145.98033

predicted

DeepCCS 1.0 [2019][M+Na]+153.7147241

predicted

DarkChem Lite v0.1.0[M+Na]+151.9368

predicted

DeepCCS 1.0 [2019]

Targets

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Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.

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KindProteinOrganismHumansPharmacological action

Yes

Actions

Inhibitor

General FunctionPyridoxal phosphate bindingSpecific FunctionCatalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine [DOPA] to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.Gene NameDDCUniprot IDP20711Uniprot NameAromatic-L-amino-acid decarboxylaseMolecular Weight53925.815 Da

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]

KindProteinOrganismHumansPharmacological action

Yes

Actions

Agonist

General FunctionThioesterase bindingSpecific FunctionAlpha-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 NameADRA2AUniprot IDP08913Uniprot NameAlpha-2A adrenergic receptorMolecular Weight48956.275 Da

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]

Enzymes

KindProteinOrganismHumansPharmacological action

No

Actions

Substrate

General FunctionO-methyltransferase activitySpecific FunctionCatalyzes 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 NameCOMTUniprot IDP21964Uniprot NameCatechol O-methyltransferaseMolecular Weight30036.77 Da

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]

KindProteinOrganismHumansPharmacological action

Unknown

Actions

Substrate

General FunctionPyridoxal phosphate bindingSpecific FunctionCatalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine [DOPA] to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.Gene NameDDCUniprot IDP20711Uniprot NameAromatic-L-amino-acid decarboxylaseMolecular Weight53925.815 Da

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]

KindProtein groupOrganismHumansPharmacological action

No

Actions

Substrate

General FunctionSulfotransferase activitySpecific FunctionSulfotransferase 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.

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]

KindProteinOrganismHumansPharmacological action

No

Actions

Substrate

General FunctionL-ascorbic acid bindingSpecific FunctionConversion of dopamine to noradrenaline.Gene NameDBHUniprot IDP09172Uniprot NameDopamine beta-hydroxylaseMolecular Weight69064.45 Da

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]

KindProteinOrganismHumansPharmacological action

No

Actions

Substrate

General FunctionPhenylethanolamine n-methyltransferase activitySpecific FunctionConverts noradrenaline to adrenaline.Gene NamePNMTUniprot IDP11086Uniprot NamePhenylethanolamine N-methyltransferaseMolecular Weight30854.745 Da

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

KindProteinOrganismHumansPharmacological action

No

Actions

Binder

General FunctionToxic substance bindingSpecific FunctionSerum 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 NameALBUniprot IDP02768Uniprot NameSerum albuminMolecular Weight69365.94 Da

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

KindProteinOrganismHumansPharmacological action

Unknown

Actions

Inhibitor

General FunctionProton-dependent oligopeptide secondary active transmembrane transporter activitySpecific FunctionProton-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 NameSLC15A1Uniprot IDP46059Uniprot NameSolute carrier family 15 member 1Molecular Weight78805.265 Da