Medication used to treat high blood pressure
Pharmaceutical compound
Methyldopa Clinical data Trade names Aldomet, Aldoril, Dopamet, others Other names α-Methyl-L -DOPA; α-Methyl-levodopa; α-Methyl-DOPA;L -α-Methyl-3,4-dihydroxyphenylalanine AHFS /Drugs.com Monograph MedlinePlus a682242 License data Pregnancy Routes of By mouth ,intravenous ATC code Legal status Legal status Pharmacokinetic dataBioavailability ~50% Metabolism Liver Onset of action 4–6 hours[ 1] Eliminationhalf-life 105 minutes Duration of action 10–48 hours[ 1] Excretion Kidney for metabolitesIdentifiers CAS Number PubChem CID IUPHAR/BPS DrugBank ChemSpider UNII KEGG ChEMBL CompTox Dashboard (EPA) ECHA InfoCard 100.008.264 Chemical and physical data Formula C 10 H 13 N O 4 Molar mass −1 3D model (JSmol ) 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
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Methyldopa , also known asα-methyl-L -DOPA and sold under the brand nameAldomet among others, is amedication used forhigh blood pressure .[ 1] high blood pressure in pregnancy .[ 1] very high blood pressure resulting in symptoms other medications are typically preferred.[ 1] by mouth orinjection into a vein .[ 1] [ 1]
Common side effects include sleepiness.[ 1] red blood cell breakdown , liver problems, andallergic reactions .[ 1] alpha-2 adrenergic receptor agonist family of medication. It works by stimulating the brain to decrease the activity of thesympathetic nervous system .[ 1]
Methyldopa was discovered in 1960.[ 2] World Health Organization's List of Essential Medicines .[ 3]
Methyldopa is used in theclinical treatment of the followingdisorders :
Methyldopa is capable of inducing a number of adverse side effects, which range from mild to severe. Nevertheless, they are generally mild when the dose is less than 1 gram per day.[ 5]
Psychological[citation needed Physiological[citation needed Dizziness ,lightheadedness , orvertigo Miosis orpupil constriction Xerostomia ordry mouth Gastrointestinal disturbances such asdiarrhea orconstipation Headache ormigraine Myalgia ormuscle aches ,arthralgia orjoint pain , orparesthesia ("pins and needles")Restless legs syndrome (RLS)Parkinsonian symptoms such asmuscle tremors ,rigidity ,hypokinesia , orbalance or postural instability Akathisia ,ataxia ,dyskinesia , as well as eventardive dyskinesia ordystonia Bell's palsy orfacial paralysis Sexual dysfunction Hyperprolactinemia Bradycardia Hypotension Orthostatic hypotension Hepatitis ,hepatotoxicity , orliver dysfunction ordamage Pancreatitis Warm autoimmune hemolytic anemia ordeficiency inred blood cells (RBCs)Myelotoxicity orbone marrow suppression , potentially leading tothrombocytopenia ,blood platelet deficiency ,leukopenia , orwhite blood cell deficiency Hypersensitivity (e.g.,lupus erythematosus ,myocarditis , orpericarditis )Lichenoid reactions (e.g.,skin lesions orrashes )Pallor Rebound hypertension viawithdrawal on account oftolerance upon the abrupt discontinuation of methyldopa has been reported.[ 6]
Mechanism of action [ edit ] The mechanism of action of methyldopa is not fully clear. It may reduce thedopaminergic andserotonergic transmission in the central andperipheral nervous system and it indirectly affectsnorepinephrine (noradrenaline) synthesis by way of inhibiting dopamine synthesis. Methyldopa acts onalpha-2 adrenergic receptors , which are found on the pre synaptic nerve terminal.[ 1]
The S-enantiomer of methyldopa is a competitive inhibitor of theenzyme aromaticL -amino acid decarboxylase (LAAD), which convertsL -DOPAdopamine .L -DOPA can cross theblood–brain barrier and thus methyldopa may have similar effects. LAAD converts it intoalpha-methyldopamine , a false precursor to norepinephrine, which in turn reduces synthesis of norepinephrine in the vesicles.Dopamine beta hydroxylase (DBH) converts alpha-methyldopamine intoalpha-methylnorepinephrine , which is anagonist of the presynapticα2 -adrenergic receptor causing inhibition of neurotransmitter release.
Methyldopa has been found to be amonoamine depleting agent .[ 7]
Maximum decrease in blood pressure occurs 4–6 hours after oral dosage. The half-life of methyldopa is 105 minutes.[ 8] absorption from thegastrointestinal tract . It ismetabolized in theliver andintestines and isexcreted inurine .[citation needed
When methyldopa was first introduced, it was the mainstay of antihypertensivetreatment , but its use has declined on account of relatively severe adverse side effects, with increased use of other safer and more tolerable agents such asalpha blockers ,beta blockers , andcalcium channel blockers . Additionally, it has yet to be associated with reducing adverse cardiovascular events including myocardial infarction and stroke, or overall all-cause mortality reduction in clinical trials.[ 9] pregnancy-induced hypertension (PIH), as it is relatively safe inpregnancy compared to many other antihypertensives which may affect thefetus .[citation needed
Difluoromethyldopa D -DOPAL -DOPAL -DOPSDopamine (Intropan, Inovan, Revivan, Rivimine, Dopastat, Dynatra, etc.)Norepinephrine (noradrenaline; Levophed, etc.)Epinephrine (adrenaline; Adrenalin, EpiPed, Twinject, etc.)MK-872 HCl salt: [55943-64-1]α-Methyltyrosine α-Methyl-5-hydroxytryptophan
α1
Agonists Antagonists Abanoquil ADRIANA Ajmalicine Alfuzosin Anisodamine Anisodine Atiprosin Atypical antipsychotics (e.g.,brexpiprazole ,clozapine ,olanzapine ,quetiapine ,risperidone )Benoxathian Beta blockers (e.g.,adimolol ,amosulalol ,arotinolol ,carvedilol ,eugenodilol ,labetalol )Buflomedil Bunazosin Corynanthine Dapiprazole Domesticine Doxazosin Ergolines (e.g.,acetergamine ,ergotamine ,dihydroergotamine ,lisuride ,nicergoline ,terguride )Etoperidone Fenspiride Hydroxyzine Indoramin Ketanserin L-765,314 mCPP Mepiprazole Metazosin Monatepil Moxisylyte Naftopidil Nantenine Neldazosin Niaprazine Niguldipine Pardoprunox Pelanserin Perlapine Phendioxan Phenoxybenzamine Phentolamine Phenylpiperazine antidepressants (e.g.,hydroxynefazodone ,nefazodone ,trazodone ,triazoledione )Piperoxan Prazosin Quinazosin Quinidine Silodosin Spegatrine Spiperone Talipexole Tamsulosin Terazosin Tiodazosin Tolazoline Tetracyclic antidepressants (e.g.,amoxapine ,maprotiline ,mianserin )Tricyclic antidepressants (e.g.,amitriptyline ,clomipramine ,doxepin ,imipramine ,trimipramine )Trimazosin Typical antipsychotics (e.g.,chlorpromazine ,fluphenazine ,loxapine ,thioridazine )Urapidil WB-4101 Zolertine
α2
Agonists Antagonists 1-PP Adimolol Amesergide Aptazapine Atipamezole Atypical antipsychotics (e.g.,asenapine ,brexpiprazole ,clozapine ,lurasidone ,olanzapine ,paliperidone ,quetiapine ,risperidone ,zotepine )Azapirones (e.g.,buspirone ,gepirone ,ipsapirone ,tandospirone )BRL-44408 Buflomedil Cirazoline Efaroxan Esmirtazapine Fenmetozole Fluparoxan Idazoxan Ketanserin Lisuride mCPP Mianserin Mirtazapine NAN-190 Pardoprunox Phentolamine Phenoxybenzamine Piperoxan Piribedil Rauwolscine Rotigotine Setiptiline Spegatrine Spiroxatrine Sunepitron Terguride Tolazoline Typical antipsychotics (e.g.,chlorpromazine ,fluphenazine ,loxapine ,thioridazine )Yohimbine
β
Phenethylamines Amphetamines Phentermines Cathinones Phenylisobutylamines (and further-extended) Catecholamines (and close relatives) Cyclized
Phenylalkylpyrrolidines 2-Benzylpiperidines (phenidates ) Phenylmorpholines (phenmetrazines) Phenyloxazolamines (aminorexes) Isoquinolines andtetrahydroisoquinolines 2-Aminoindanes 2-Aminotetralins Others / unsorted 1-Aminomethylindanes (e.g.,2CB-Ind ,AMMI ,bromojimscaline ,jimscaline )2-ADN 2-Benzhydrylpyrrolidine 2C-B-5-hemiFLY-α6 (BNAP) 2C-B-PYR 2CBecca 2CB7 2CJP 2CLisaB 2CLisaH 3-Benzazepines (e.g.,fenoldopam ,lorcaserin ,7-chlorolorcaserin ,SCHEMBL5334361 )3-Benzhydrylmorpholine 3-Phenylpiperidines (e.g.,3-phenylpiperidine ,3-PPP ,OSU-6162 (PNU-96391) ,LPH-5 ,LPH-48 ,Z3517967757 (Z7757) )6-AB AL-1095 Aminochromes (e.g.,adrenochrome ,adrenolutin )Benzocyclobutenes (e.g.,2CBCB-NBOMe ,bromotomscaline ,S33005 ,TCB-2 ,tomscaline )Benzoxepins (e.g.,BBOX ,IBOX ,TFMBOX )Butyltolylquinuclidine Camfetamine Cypenamine (trans -2-phenylcyclopentylamine) Diphenidine Diphenylprolinol DMBMPP Ergolines (e.g.,LSD )Fencamfamin GYKI-52895 HDMP-29 Ivabradine Methoxphenidine Methylmorphenate Milnacipran MT-45 2-Naphthylamine Org 6582 Partial ergolines (e.g.,NDTDI ,RU-27849 ,DEIMDHPCA ,DEMPDHPCA ,DEMPDHPCA-2C-D ,RU-27251 )PF-592,379 Phenylcyclopropylamines (e.g.,DMCPA ,TMT ,tranylcypromine )Phenylpiracetams (e.g.,phenylpiracetam ,MRZ-9547 ,RGPU-95 )Pyridopyrroloquinoxalines (e.g.,lumateperone ,deulumateperone ,IHCH-7079 ,IHCH-7086 ,IHCH-7113 ,ITI-1549 )Tetrahydrobenzopyranylamines (e.g.,CT-5126 )Tolazoline Tricyclics (e.g.,AMDA ,AMDH ,benzoctamine ,dizocilpine ,SpAMDA )ZC-B
Related compounds 2-Furylethylamine 2-Pyrrolylethylamine 3-Pyrrolylethylamine 3-Pyrrolylpropylamine 2-Tetrahydrofurylethylamine 4-Benzylpiperidine 7-AB Alkylamines (e.g.,1,3-DMBA Tooltip 1,3-dimethylbutylamine ,1,4-DMAA Tooltip 1,4-dimethylamylamine ,heptaminol ,iproheptine ,isometheptene ,methylhexanamine/ 1,3-DMAA ,octodrine ,oenethyl ,tuaminoheptane )Benzylamines (e.g.,benzylamine ,α-methylbenzylamine ,MDM1EA ,ALPHA ,M-ALPHA ,pargyline )Benzylpiperazines (e.g.,benzylpiperazine ,MDBZP ,fipexide )Cyclohexylaminopropanes (e.g.,propylhexedrine ,norpropylhexedrine )Cyclopentylaminopropanes (e.g.,isocyclamine ,cyclopentamine )Phenoxyethylamines (e.g.,3,4,5-trimethoxyphenoxyethylamine ,CT-4719 ,ORG-37684 )Phenylalkenylamines (e.g.,phenylbutenamine )Phenylalkynylamines (e.g.,phenylbutynamine )Phenylpiperazines (e.g.,1-phenylpiperazine ,mCPP Tooltip meta-chlorophenylpiperazine ,TFMPP Tooltip trifluoromethylphenylpiperazine ,oMPP Tooltip ortho-methylphenylpiperazine ,pFPP Tooltip para-fluorophenylpiperazine ,pMeOPP Tooltip para-methoxyphenylpiperazine )Phenylpropylamines (e.g.,phenylpropylamine ,homo-MDA ,homo-MDMA )Thienylaminopropanes (thiopropamines) (e.g.,thiopropamine ,methiopropamine ,thiothinone )
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