| Revision as of 12:23, 24 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456724425 of page Methyldopa for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL'). |
Latest revision as of 07:35, 8 October 2024 edit 76.174.0.57 (talk) See also. |
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{{Short description|Medication used to treat high blood pressure}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Drugbox |
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{{Drugbox |
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| Verifiedfields = changed |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 406734025 |
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| verifiedrevid = 462251064 |
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| IUPAC_name = (''S'')-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid |
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| IUPAC_name = (''S'')-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid |
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| image = (S)-Methyldopa Structural Formulae V.1.svg |
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| image = Methyldopa.svg |
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| alt = Skeletal formula of methyldopa |
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| image2 = Methyldopa molecule ball.png |
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| alt2 = Ball-and-stick model of the methyldopa molecule |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| tradename = |
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| tradename = Aldomet, Aldoril, Dopamet, others |
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| Drugs.com = {{drugs.com|monograph|methyldopa}} |
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| Drugs.com = {{drugs.com|monograph|methyldopa}} |
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| MedlinePlus = a682242 |
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| MedlinePlus = a682242 |
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| DailyMedID = Methyldopa |
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| pregnancy_category = a drug of choice in ] |
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| legal_status = Rx-only |
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| pregnancy_AU = A |
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| legal_AU = S4 |
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| routes_of_administration = Oral, ] |
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| legal_CA = Rx-only |
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| legal_UK = POM |
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| legal_US = Rx-only |
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| routes_of_administration = ], ] |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| bioavailability = approximately 50% |
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| bioavailability = approximately 50% |
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| onset = 4 to 6 hrs<ref name=AHFS2016/> |
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| metabolism = ] |
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| metabolism = ] |
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| elimination_half-life = 105 minutes |
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| elimination_half-life = 105 minutes |
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| duration_of_action = 10 to 48 hrs<ref name=AHFS2016/> |
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| excretion = ] for metabolites |
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| excretion = ] for metabolites |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| index_label = |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| index2_label = anhydrous |
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| CAS_number2_Ref = {{cascite|correct|CAS}} |
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| CAS_number2 = 555-30-6 |
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| UNII2_Ref = {{fdacite|correct|FDA}} |
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| UNII2 = M4R0H12F6M |
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| IUPHAR_ligand = 5217 |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 555-30-6 |
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| CAS_number = 41372-08-1 |
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| ATC_prefix = C02 |
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| ATC_prefix = C02 |
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| ATC_suffix = AB01 |
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| ATC_suffix = AB01 |
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| ATC_supplemental = <br />{{ATC|C02|AB02}} (]) |
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| PubChem = 40175 |
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| PubChem2 = 40175 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB00968 |
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| DrugBank = DB00968 |
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| KEGG = D00405 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 36713 |
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| PubChem = 38853 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 35562 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 56LH93261Y |
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| UNII = 56LH93261Y |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = <!-- blanked - oldvalue: 459 --> |
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| ChEMBL = 459 |
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| synonyms = α-Methyl-<small>L</small>-DOPA; α-Methyl-levodopa; α-Methyl-DOPA; <small>L</small>-α-Methyl-3,4-dihydroxyphenylalanine |
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| C=10 | H=13 | N=1 | O=4 |
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| molecular_weight = 211.215 g/mol |
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<!--Chemical data--> |
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| smiles = O=C(O)C(NC)Cc1cc(O)c(O)cc1 |
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| C=10 | H=13 | N=1 | O=4 |
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| InChI = 1/C10H13NO4/c1-11-7(10(14)15)4-6-2-3-8(12)9(13)5-6/h2-3,5,7,11-13H,4H2,1H3,(H,14,15) |
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| smiles = C(N)(Cc1ccc(O)c(O)c1)C(=O)O |
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| InChIKey = QZIWDCLHLOADPK-UHFFFAOYAI |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C10H13NO4/c1-11-7(10(14)15)4-6-2-3-8(12)9(13)5-6/h2-3,5,7,11-13H,4H2,1H3,(H,14,15) |
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| StdInChI = 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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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = QZIWDCLHLOADPK-UHFFFAOYSA-N |
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| StdInChIKey = CJCSPKMFHVPWAR-JTQLQIEISA-N |
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}} |
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}} |
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<!-- Definition and medical uses --> |
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'''Methyldopa''', also known as '''α-methyl-<small>L</small>-DOPA''' and sold under the brand name '''Aldomet''' among others, is a ] used for ].<ref name="AHFS2016" /> It is one of the preferred treatments for ].<ref name="AHFS2016" /> For other types of high blood pressure including ] other medications are typically preferred.<ref name="AHFS2016" /> It can be given ] or ].<ref name=AHFS2016/> Onset of effects is around 5 hours and they last about a day.<ref name="AHFS2016">{{cite web|title=Methyldopa|url=https://www.drugs.com/monograph/methyldopa.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221010844/https://www.drugs.com/monograph/methyldopa.html|archive-date=21 December 2016}}</ref> |
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<!-- Side effects and mechanism --> |
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Common side effects include sleepiness.<ref name=AHFS2016/> More severe side effects include ], liver problems, and ].<ref name=AHFS2016/> Methyldopa is in the ] family of medication. It works by stimulating the brain to decrease the activity of the ].<ref name=AHFS2016/> |
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<!-- Society and culture --> |
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Methyldopa was discovered in 1960.<ref name=Wal2012>{{cite book| vauthors = Walker RS |title=Trends and Changes in Drug Research and Development|date=2012|publisher=Springer Science & Business Media|isbn=9789400926592|page=109|url=https://books.google.com/books?id=FB_2CAAAQBAJ&pg=PA109|language=en|url-status=live|archive-url=https://web.archive.org/web/20160914021552/https://books.google.ca/books?id=FB_2CAAAQBAJ&pg=PA109|archive-date=2016-09-14}}</ref> It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> |
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== Medical uses == |
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Methyldopa is used in the ] of the following ]s: |
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* ] (or high blood pressure) |
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* ] (or pregnancy-induced hypertension) and ].<ref>{{Cite book| vauthors = Malha L, Podymow T, August P |chapter-url=https://www.sciencedirect.com/science/article/pii/B9780323429733000391|title=Hypertension: A Companion to Braunwald's Heart Disease|publisher=]|year=2018|isbn=978-0-323-42973-3|edition=3rd|pages=361–373|language=en|chapter=39 - Hypertension in Pregnancy|doi=10.1016/B978-0-323-42973-3.00039-1}}</ref> |
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== Side effects == |
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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.<ref>{{cite book |title=] |date=September 2008 |pages= |isbn=978-0-85369-778-7 }}</ref> Side effects may include: |
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* Psychological |
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** ] or even ], as well as ]s |
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** ] or ], as well as ] |
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** ], especially of the ] variant |
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** Decreased ], ], and ] |
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** Impaired ], ], and ] |
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** Decreased ], ], and ] |
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** ] or ] or ] or ] |
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** ] or ] or ] or ] |
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** ] or ] |
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** ] |
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** ] or ], as well as mild ] |
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** ] including impaired ], ], and ] |
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* Physiological |
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** ], ], or ] |
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** ] or ] |
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** ] or ] |
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** ]s such as ] or ] |
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** ] or ] |
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** ] or ]s, ] or ], or ] ("pins and needles") |
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** ] (RLS) |
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** ] ]s such as ]s, ], ], or ] |
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** ], ], ] as well as even ], or ] |
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** ] or ] ] |
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** ] consisting of impaired ] or ] |
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** ] or excess ], ]/breast enlargement in ]s, or ] or absence of ]s in ]s |
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** ] or decreased ] |
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** ] or decreased ] (though this may also be considered a ]) |
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** ] (also known as ]) |
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** ], ], or ] ] or ] |
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** ] or ] of the ] |
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** ] or ] in ]s (RBCs) |
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** ] or ], potentially leading to ] or ] ] or ] or ] (WBC) ] |
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** ] such as ], ], or ] |
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** ]s such as ]s or ]es |
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** ] |
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=== Rebound/withdrawal === |
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] ] via ] on account of ] upon the abrupt discontinuation of methyldopa has been reported.<ref> {{webarchive|url=https://web.archive.org/web/20080313130358/http://www.inchem.org/documents/pims/pharm/methyldo.htm |date=2008-03-13 }}</ref> |
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== Mechanism of action == |
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The mechanism of action of methyldopa is not fully clear. Although it is a ] ], it does not block reuptake or transporters. It may reduce the ] and ] transmission in the ] and it indirectly affects ] (noradrenaline) synthesis. Methyldopa acts on ], which are found on the pre synaptic nerve terminal.<ref name="AHFS2016" /> This inhibits the synthesis of ] by inhibiting ]. |
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The S-enantiomer of methyldopa is a competitive inhibitor of the ] ] (LAAD), which converts ] into ]. <small>L</small>-DOPA can cross the ] and thus methyldopa may have similar effects. LAAD converts it into ], a false prescursor to norepinephrine, which in turn reduces synthesis of norepinephrine in the vesicles. ] (DBH) converts alpha-methyldopamine into ], which is an ] of the presynaptic ] causing inhibition of neurotransmitter release. |
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Methyldopa has been found to be a ].<ref name="TungGoldbergHollister1988">{{cite journal | vauthors = Tung CS, Goldberg MR, Hollister AS, Sweetman BJ, Robertson D | title = Depletion of brainstem epinephrine stores by alpha-methyldopa: possible relation to attenuated sympathetic outflow | journal = Life Sci | volume = 42 | issue = 23 | pages = 2365–2371 | date = 1988 | pmid = 3287081 | doi = 10.1016/0024-3205(88)90190-7 | url = }}</ref> |
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== Pharmacokinetics == |
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Maximum decrease in blood pressure occurs 4-6 hours after oral dosage. The half-life of methyldopa is 105 minutes.<ref>{{Cite web |title=DailyMed - METHYLDOPA tablet, film coated |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00206aae-7db1-4ae9-8500-b03fd6788d74 |access-date=2022-07-25 |website=dailymed.nlm.nih.gov}}</ref> Methyldopa exhibits variable ] from the ]. It is ] in the ] and ]s and is ] in ]. |
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== History == |
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When methyldopa was first introduced, it was the mainstay of antihypertensive ], 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 ]s, ]s, and ]s. 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.<ref name="pmid19821316">{{cite journal | vauthors = Mah GT, Tejani AM, Musini VM | title = Methyldopa for primary hypertension | journal = The Cochrane Database of Systematic Reviews | volume = 2009 | issue = 4 | pages = CD003893 | date = October 2009 | pmid = 19821316 | pmc = 7154320 | doi = 10.1002/14651858.CD003893.pub3 }}</ref> Nonetheless, one of methyldopa's still current indications is in the management of ] (PIH), as it is relatively safe in ] compared to many other antihypertensives which may affect the ]. |
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== See also == |
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* ] |
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* ] (dextrodopa) |
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* ] (levodopa; trade names Sinemet, Pharmacopa, Atamet, Stalevo, Madopar, Prolopa, etc.) |
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* ] (droxidopa) |
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* ] (Intropan, Inovan, Revivan, Rivimine, Dopastat, Dynatra, etc.) |
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* ] (noradrenaline; Levophed, etc.) |
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* ] (adrenaline; Adrenalin, EpiPed, Twinject, etc.) |
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* HCl salt: |
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* ] |
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* ] |
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== References == |
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{{Reflist}} |
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== External links == |
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{{Commons category|Methyldopa}} |
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{{Antihypertensives and diuretics}} |
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{{Antiparkinson}} |
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{{Adrenergic receptor modulators}} |
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{{Monoamine metabolism modulators}} |
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{{Phenethylamines}} |
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{{portal bar|Medicine}} |
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