Metaraminol

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.^[1][3][4] It is given by intramuscular or intravenous administration.^[1]

Metaraminol

Clinical data
Trade names	Aramine, Metaramin, Pressonex, others
Other names	Metaradrine; Hydroxynorephedrine; m-Hydroxypropadrine; m-Hydroxynorephedrine; meta-Hydroxynorephedrine; 3-Hydroxyphenylisopropanolamine; (1R,2S)-3,β-Dihydroxy-α-methylphenethylamine; (1R,2S)-3,β-Dihydroxyamphetamine
AHFS/Drugs.com	International Drug Names
License data	US DailyMed: Metaraminol
Pregnancy category	AU: C
Routes of administration	Intramuscular injection, intravenous administration[1]
Drug class	Norepinephrine releasing agent; Adrenergic receptor agonist; Sympathomimetic; Antihypotensive
ATC code	C01CA09 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) US: ℞-only[1][2]
Pharmacokinetic data
Protein binding	45%
Metabolism	Liver
Identifiers
IUPAC name (1R,2S)-3-[-2-amino-1-hydroxy-propyl]phenol
CAS Number	54-49-9 Y 33402-03-8 (bitartrate)
PubChem CID	5906
IUPHAR/BPS	7229
DrugBank	DB00610 Y
ChemSpider	5695 Y
UNII	818U2PZ2EH
KEGG	D08192 Y
ChEBI	CHEBI:6794 Y
ChEMBL	ChEMBL1201319 Y
CompTox Dashboard (EPA)	DTXSID8023268
Chemical and physical data
Formula	C9H13NO2
Molar mass	167.208 g·mol−1
3D model (JSmol)	Interactive image
SMILES O[C@H](c1cc(O)ccc1)[C@@H](N)C
InChI InChI=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 Y Key:WXFIGDLSSYIKKV-RCOVLWMOSA-N Y
(verify)

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.^[5][6][7] It is a substituted amphetamine and is closely related to phenylpropanolamine, ephedrine, and oxilofrine.^[3][4]

Metaraminol was approved for medical use in the United States in September 1954.^[8][9][10]

Medical uses

A commercially prepared pre-filled syringe of metaraminol for bolus use during anaesthesia, made up as 0.5 mg/mL (2.5 mg in 5 mL).

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.^[11][12]

Metaraminol is also used in the treatment of priapism.^[13][14][15]

Pharmacology

Pharmacodynamics

The dominant mechanism of action for the vasopressor action of metaraminol is indirect,^[5] with metaraminol displacing norepinephrine from neuronal vesicles in order for the noradrenaline to exert these effects.^[6] Metaraminol at higher doses may have direct α-adrenergic agonist and β₁-adrenergic agonist effects.^[5] 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.^[3][4] It is the (1R,2S)-enantiomer of meta-hydroxynorephedrine (3,β-dihydroxyamphetamine).^[3][4] 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).^[3][4]

The experimental log P of metaraminol is -0.27 and its predicted log P ranges from -0.59 to 0.07.^[16][17]

Metaraminol is used pharmaceutically as the bitartrate salt.^[3][4]

History

Metaraminol was approved for medical use in the United States in September 1954.^{[8][9][10][3]}

Society and culture

Names

Metaraminol is the generic name of the medication and its INNTooltip International Nonproprietary Name and BANTooltip British Approved Name, while its DCFTooltip Dénomination Commune Française is métaraminol and its DCITTooltip Denominazione Comune Italiana is metaraminolo.^[3][4][18] As the bitartrate salt, its generic name is metaraminol bitartrate and this is its USANTooltip United States Adopted Name and JANTooltip Japanese Accepted Name, while metaraminol tartrate is its BANMTooltip British Approved Name.^[3][4][18] A synonym of metaraminol is metaradrine.^[4][18] Brand names of metaraminol include Aramin, Aramine, and Pressonex, among others.^[3][4][18]