metaraminol

{{Short description|Antihypotensive medication}}

{{Use dmy dates|date=April 2025}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Infobox drug

| Verifiedfields = verified

| verifiedrevid = 462249333

| image = Metaraminol Structural Formulae.png

| width = 225

| pronounce =

| tradename = Aramine, Metaramin, Pressonex, others

| Drugs.com = {{drugs.com|international|metaraminol}}

| MedlinePlus =

| DailyMedID = Metaraminol

| pregnancy_AU = C

| pregnancy_AU_comment =

| pregnancy_category=

| routes_of_administration = Intramuscular injection, intravenous administration

| class = Norepinephrine releasing agent; Adrenergic receptor agonist; Sympathomimetic; Antihypotensive

| ATC_prefix = C01

| ATC_suffix = CA09

| ATC_supplemental =

| legal_AU = S4

| legal_AU_comment =

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| legal_DE =

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| legal_NZ =

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| legal_UK = POM

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment = {{cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/009509s026lbl.pdf|title=Injection : Aramine (Metaraminol Bitartrate)|website=U.S. Food and Drug Administration (FDA) |access-date=12 March 2022}}{{cite web | title=Metaraminol Bitartrate Injection, USP | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=813743 | access-date=12 April 2025}}

| legal_EU =

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| bioavailability =

| protein_bound = 45%

| metabolism = Liver

| elimination_half-life =

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| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 54-49-9

| CAS_supplemental =
33402-03-8 (bitartrate)

| PubChem = 5906

| IUPHAR_ligand = 7229

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00610

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 5695

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 818U2PZ2EH

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D08192

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 6794

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 1201319

| synonyms = Metaradrine; Hydroxynorephedrine; m-Hydroxypropadrine; m-Hydroxynorephedrine; meta-Hydroxynorephedrine; 3-Hydroxyphenylisopropanolamine; (1R,2S)-3,β-Dihydroxy-α-methylphenethylamine; (1R,2S)-3,β-Dihydroxyamphetamine

| IUPAC_name = (1R,2S)-3-[-2-amino-1-hydroxy-propyl]phenol

| C=9 | H=13 | N=1 | O=2

| SMILES = O[C@H](c1cc(O)ccc1)[C@@H](N)C

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C9H13NO2/c1-6(10)9(12)7-3-2-4-8(11)5-7/h2-6,9,11-12H,10H2,1H3/t6-,9-/m0/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = WXFIGDLSSYIKKV-RCOVLWMOSA-N

}}

Metaraminol, also known as metaradrine and sold under the brand name Aramine among others, is a sympathomimetic medication which is used in the prevention and treatment of hypotension (low blood pressure), particularly as a complication of anesthesia.https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/009509s026lbl.pdf It is given by intramuscular or intravenous administration.

Side effects of metaraminol include reflex bradycardia among others. Metaraminol is a norepinephrine releasing agent and at high doses a α1-adrenergic receptor agonist with some β-adrenergic effect.{{cite journal | vauthors = Kee VR | date = Aug 2003 | title = Hemodynamic pharmacology of intravenous vasopressors | url = http://ccn.aacnjournals.org/content/23/4/79.long | journal = Crit Care Nurse | volume = 23 | issue = 4| pages = 79–82 | pmid = 12961786 | doi = 10.4037/ccn2003.23.4.79 }} It is a substituted amphetamine and is closely related to phenylpropanolamine, ephedrine, and oxilofrine.

Metaraminol was approved for medical use in the United States in September 1954.{{cite web | title=Aaramine: FDA-Approved Drugs | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=009509 | access-date=12 April 2025}}

Medical uses

File:Metaraminol prefilledsyringe.jpg

Metaraminol is given intravenously as either a bolus (often 0.5–1 mg doses) or as an infusion, usually via peripheral intravenous access. Metaraminol is commonly available as 10 mg in 1 mL, that requires dilution prior to administration (often made up to a 0.5 mg/mL solution), however pre-prepared syringes of metaraminol for bolus use for hypotension are also commonly available.{{Cite web |title=Metaraminol 0.5 mg/ml, Solution for Injection in pre-filled syringe - Summary of Product Characteristics (SmPC) - (emc) |url=https://www.medicines.org.uk/emc/product/11698/smpc |access-date=19 October 2022 |website=www.medicines.org.uk}}{{Cite journal | vauthors = Goodrick N, Wentrup T, Messer G, Gleeson P, Culwick M, Goulding G |title=Pre-filled emergency drugs: The introduction of pre-filled metaraminol and ephedrine syringes into the main operating theatres of a major metropolitan centre | url=https://search.informit.org/doi/abs/10.3316/INFORMIT.477021141406775 |journal=Australasian Anaesthesia |date=21 August 2020 |issue=2013 |pages=127–134 }}

Metaraminol is also used in the treatment of priapism.{{cite journal |vauthors=McDonald M, Santucci R | title = Successful management of stuttering priapism using home self-injections of the alpha-agonist metaraminol. | journal = Int Braz J Urol | volume = 30 | issue = 2 | pages = 121–122 | year = 2004 | pmid = 15703094 | doi = 10.1590/S1677-55382004000200007| doi-access = free }}{{cite journal |vauthors=Koga S, Shiraishi K, Saito Y | title = Post-traumatic priapism treated with metaraminol bitartrate: case report. | journal = J Trauma | volume = 30 | issue = 12 | pages = 1591–3 | year = 1990 | pmid = 2258979 | doi = 10.1097/00005373-199012000-00029}}{{cite journal |vauthors=Block T, Sturm W, Ernst G, Staehler G, Schmiedt E | title = [Metaraminol in therapy of various forms of priapism] | journal = Urologe A | volume = 27 | issue = 4 | pages = 225–9 | year = 1988 | pmid = 3140463}}

Pharmacology

=Pharmacodynamics=

The dominant mechanism of action for the vasopressor action of metaraminol is indirect,{{Cite web |title=Metaraminol | work = Deranged Physiology |url=https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20979/metaraminol |access-date=19 October 2022 |language=en}} with metaraminol displacing norepinephrine from neuronal vesicles in order for the noradrenaline to exert these effects.{{cite journal | vauthors = Harrison DC, Chidsey CA, Braunwald E | title = Studies on the Mechanism of Action of Metaraminol (Aramine) | journal = Annals of Internal Medicine | volume = 59 | issue = 3| pages = 297–305 | date = September 1963 | pmid = 14065947 | doi = 10.7326/0003-4819-59-3-297 }} Metaraminol at higher doses may have direct α-adrenergic agonist and β1-adrenergic agonist effects. However at doses common in clinical practice, the indirect α1-adrenergic effects predominate, such that reflex bradycardia is a common side effect.

Chemistry

Metaraminol, also known as (1R,2S)-3,β-dihydroxy-α-methylphenethylamine or as (1R,2S)-3,β-dihydroxyamphetamine, is a substituted phenethylamine and amphetamine derivative.{{cite book | last=Elks | first=J. | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA62 | access-date=31 August 2024 | page=62}}{{cite book | author=Schweizerischer Apotheker-Verein | title=Index Nominum 2000: International Drug Directory | publisher=Medpharm Scientific Publishers | series=Index nominum | year=2000 | isbn=978-3-88763-075-1 | url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA660 | access-date=31 August 2024 | page=660}} It is the (1R,2S)-enantiomer of meta-hydroxynorephedrine (3,β-dihydroxyamphetamine). The drug is closely related to phenylpropanolamine ((1RS,2SR)-β-hydroxyamphetamine; norephedrine), ephedrine ((1R,2S)-β-hydroxy-N-methylamphetamine), para-hydroxynorephedrine (4,β-dihydroxyamphetamine), and oxilofrine (4,β-dihydroxy-N-methylamphetamine).

The experimental log P of metaraminol is -0.27 and its predicted log P ranges from -0.59 to 0.07.{{cite web | title=Metaraminol | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/5906 | access-date=1 September 2024}}{{cite web | title=Metaraminol | website=ChemSpider | date=1 September 2024 | url=https://www.chemspider.com/Chemical-Structure.5695.html | access-date=1 September 2024}}

Metaraminol is used pharmaceutically as the bitartrate salt.

History

Metaraminol was approved for medical use in the United States in September 1954.{{cite journal | vauthors = Weil MH, Spink WW | title = Clinical studies on a vasopressor agent: metaraminol (aramine). I. Observations in normotensive subjects | journal = Am J Med Sci | volume = 229 | issue = 6 | pages = 661–669 | date = June 1955 | pmid = 14376394 | doi = 10.1097/00000441-195506000-00008 | url = }}{{cite journal | vauthors = Weil MH | title = Clinical studies on a vasopressor agent: metaraminol (aramine). II. Observations on its use in the management of shock | journal = The American Journal of the Medical Sciences | volume = 230 | issue = 4 | pages = 357–369 | date = October 1955 | pmid = 13258566 | doi = 10.1097/00000441-195510000-00001 }}

Society and culture

=Names=

Metaraminol is the generic name of the medication and its {{Abbrlink|INN|International Nonproprietary Name}} and {{Abbrlink|BAN|British Approved Name}}, while its {{Abbrlink|DCF|Dénomination Commune Française}} is métaraminol and its {{Abbrlink|DCIT|Denominazione Comune Italiana}} is metaraminolo.https://web.archive.org/web/20160303210434/https://www.drugs.com/international/metaraminol.html As the bitartrate salt, its generic name is metaraminol bitartrate and this is its {{Abbrlink|USAN|United States Adopted Name}} and {{Abbrlink|JAN|Japanese Accepted Name}}, while metaraminol tartrate is its {{Abbrlink|BANM|British Approved Name}}. A synonym of metaraminol is metaradrine. Brand names of metaraminol include Aramin, Aramine, and Pressonex, among others.

References