Methyldopa
Medication used to treat high blood pressure
Pharmaceutical compound
Methyldopa 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 Bioavailability approximately 50% Metabolism Liver Onset of action 4 to 6 hrs[ 1] Elimination half-life 105 minutes Duration of action 10 to 48 hrs[ 1] Excretion Kidney for metabolites
(S )-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid
CAS Number PubChem CID IUPHAR/BPS DrugBank ChemSpider UNII KEGG ChEMBL CompTox Dashboard (EPA ) ECHA InfoCard 100.008.264 Formula C 10 H 13 N O 4 Molar mass −1 3D model (JSmol )
C[C@](N)(Cc1ccc(O)c(O)c1)C(=O)O
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
N Key:CJCSPKMFHVPWAR-JTQLQIEISA-N
N N Y (what is this?) (verify)
Methyldopa , also known as α-methyl-L -DOPA and sold under the brand name Aldomet among others, is a medication used for high blood pressure .[ 1] high blood pressure in pregnancy .[ 1] very high blood pressure resulting in symptoms other medications are typically preferred.[ 1] by mouth or injection into a vein .[ 1] [ 1]
Common side effects include sleepiness.[ 1] red blood cell breakdown , liver problems, and allergic reactions .[ 1] alpha-2 adrenergic receptor agonist family of medication. It works by stimulating the brain to decrease the activity of the sympathetic nervous system .[ 1]
Methyldopa was discovered in 1960.[ 2] World Health Organization's List of Essential Medicines .[ 3]
Medical uses
Methyldopa is used in the clinical treatment of the following disorders :
Side effects
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
Depression or even suicidal ideation , as well as nightmares Apathy or anhedonia , as well as dysphoria Anxiety , especially of the social anxiety variantDecreased alertness , awareness , and wakefulness
Impaired attention , focus , and concentration
Decreased desire , drive , and motivation
Fatigue or lethargy or malaise or lassitude Sedation or drowsiness or somnolence or sleepiness Agitation or restlessness Cognitive and memory impairment Derealization or depersonalization , as well as mild psychosis Sexual dysfunction including impaired libido , desire , and drive
Physiological
Dizziness , lightheadedness , or vertigo Miosis or pupil constriction Xerostomia or dry mouth Gastrointestinal disturbances such as diarrhea or constipation Headache or migraine Myalgia or muscle aches , arthralgia or joint pain , or paresthesia ("pins and needles")Restless legs syndrome (RLS)Parkinsonian symptoms such as muscle tremors , rigidity , hypokinesia , or balance or postural instability Akathisia , ataxia , dyskinesia as well as even tardive dyskinesia , or dystonia Bell's palsy or facial paralysis Sexual dysfunction consisting of impaired erectile dysfunction or anorgasmia Hyperprolactinemia or excess prolactin , gynecomastia /breast enlargement in males , or amenorrhoea or absence of menstrual cycles in females Bradycardia or decreased heart rate Hypotension or decreased blood pressure (though this may also be considered a therapeutic benefit )Orthostatic hypotension (also known as postural hypotension )Hepatitis , hepatotoxicity , or liver dysfunction or damage Pancreatitis or inflammation of the pancreas Warm autoimmune hemolytic anemia or deficiency in red blood cells (RBCs)Myelotoxicity or bone marrow suppression , potentially leading to thrombocytopenia or blood platelet deficiency or leukopenia or white blood cell (WBC) deficiency Hypersensitivity such as lupus erythematosus , myocarditis , or pericarditis Lichenoid reactions such as skin lesions or rashes Pallor
Rebound hypertension via withdrawal on account of tolerance upon the abrupt discontinuation of methyldopa has been reported.[ 6]
Mechanism of action
The mechanism of action of methyldopa is not fully clear. Although it is a centrally acting sympathomimetic , it does not block reuptake or transporters. It may reduce the dopaminergic and serotonergic transmission in the peripheral nervous system and it indirectly affects norepinephrine (noradrenaline) synthesis. Methyldopa acts on alpha-2 adrenergic receptors , which are found on the pre synaptic nerve terminal.[ 1] norepinephrine by inhibiting tyrosine hydroxylase .
The S-enantiomer of methyldopa is a competitive inhibitor of the enzyme aromatic L -amino acid decarboxylase (LAAD), which converts L -DOPAdopamine . L -DOPA can cross the blood brain barrier and thus methyldopa may have similar effects. LAAD converts it into alpha-methyldopamine , a false prescursor to norepinephrine, which in turn reduces synthesis of norepinephrine in the vesicles. Dopamine beta hydroxylase (DBH) converts alpha-methyldopamine into alpha-methylnorepinephrine , which is an agonist of the presynaptic α2-adrenergic receptor causing inhibition of neurotransmitter release.
Methyldopa has been found to be a monoamine depleting agent .[ 7]
Pharmacokinetics
Maximum decrease in blood pressure occurs 4-6 hours after oral dosage. The half-life of methyldopa is 105 minutes.[ 8] absorption from the gastrointestinal tract . It is metabolized in the liver and intestines and is excreted in urine .
History
When methyldopa was first introduced, it was the mainstay of antihypertensive treatment , but its use has declined on account of relatively severe adverse side effects, with increased use of other safer and more tolerable agents such as alpha blockers , beta blockers , and calcium 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 in pregnancy compared to many other antihypertensives which may affect the fetus .
See also
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
References
External links
Wikimedia Commons has media related to
Methyldopa .
α1
Agonists Antagonists
Abanoquil 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
