METARAMINOL

Chemical Properties

Colourless solid

Originator

Aramine,MSD, US,1952

Uses

Adrenergic.

Uses

Metaraminol is a direct and indirect non-specific adrenoceptor agonist. It acts primarily via α1-receptors, causing vasoconstriction with subsequent increase in arterial pressure and reflex bradycardia. It is administered via i.v. bolus injection at a dose of 0.5–2 mg, titrated to effect.

Uses

Metaraminol is a sympathomimetic amine of both direct and indirect action that has hemodynamic characteristics similar to norepinephrine. It has the ability to elevate both systolic and diastolic blood pressure.
It is used in hypotensive shock for the purpose of elevating blood pressure, which can result from spinal anesthesia, surgical complications, and head trauma.

Definition

ChEBI: A member of the class of phenylethanolamines that is 2-amino-1-phenylethanol substituted by a methyl group at position 2 and a phenolic hydroxy group at position 1. A sympathomimetic agent , it is used in the treatment of hypotension.

Manufacturing Process

The hydrochloride of the m-hydroxyphenylpropanolamine may be prepared by dissolving or suspending 90 parts of m-hydroxyphenylethyl ketone, O = C(C6H4-OH)-C2H5, in about 400 parts of ether. Hydrogen chloride is slowly bubbled through the solution or suspension while agitating it and 61.8 g of butyl nitrite is added during the course of 60 to 90 minutes. During the addition of the butyl nitrite the suspended m-hydroxyphenylethyl ketone gradually dissolves. The mixture or solution is allowed to stand for at least an hour, but preferably overnight. It is then repeatedly extracted with dilute alkali until all alkali-soluble material is removed. The alkaline extract is slowly acidified and the precipitate which forms is crude m-hydroxyphenyl-αoximinoethyl ketone. After recrystallization from water this melts at 138°C.
10.8 parts of the meta ketone is dissolved in about 125 parts of absolute alcohol containing 5.6 parts of hydrogen chloride. The solution is agitated with a catalyst such as the palladium catalyst above described in an atmsophere of hydrogen until no more hydrogen is absorbed. This requires from 60 to 90 minutes or more. When reduction is complete the catalyst is filtered off and the filtrate evaporated to dryness by being placed in a desiccator at ordinary temperature.
The residue is the hydrochloride of m-hydroxyphenyl-α-aminoethyl ketone. This is purified by recrystallization from absolute alcohol. It is then dissolved in 200 parts of water and agitated with a further quantity of the palladium catalyst in an atmosphere of hydrogen until saturated. The product thus recovered from the solution is the hydrochloride of m-hydroxyphenylpropanol amine. After recrystallization from absolute alcohol this melts at 177°C. The corresponding free base can be prepared from the hydrochloride by treatment with ammonia, according to US Patent 1,995,709.
Metaraminol is often used in the form of the bitartrate.

brand name

Aramine (Merck) .

Therapeutic Function

Hypertensive

General Description

Metaraminol is the N-desmethyl- -methylanalog of phenylephrine. It possesses a mixed mechanismof action, with its direct-acting effects mainly on 1-receptors. It is used parenterally as a vasopressor in thetreatment and prevention of the acute hypotensive stateoccurring with spinal anesthesia. It also has been used totreat severe hypotension brought on by other traumas thatinduce shock.

Synthesis

Metaraminol, L-1-(3-hydroxyphenyl)-2-aminopropan-1-ol (11.3.11), is synthesized in two ways. The first way is synthetic, and it is from 3-hydroxypropiophenone. The hydroxyl group is protected by alkylation with benzyl chloride, giving 3-benzyloxypropiophenone (11.3.8). Upon reaction with butylnitrite, it undergoes nitrosation into the isonitrosoketone (11.3.9), which by reduction using semisynthetic, consisting of fermentation of D-glucose in the presence of 3-acetoxybenzaldehyde, which forms (-)-1-hydroxy-1-(3-hydroxyphenyl)-acetone (11.3.12), the carbonyl group of which is reduced by hydrogen over a palladium catalyst in the presence of ammonia, giving metaraminol (11.3.11) [62¨C65].

Drug interactions

Potentially hazardous interactions with other drugs Adrenergic neurone blockers: hypotensive effect antagonised.
Anaesthetics: risk of ventricular arrhythmias with isoflurane - avoid.
Antibacterials: risk of hypertensive crisis with linezolid and tedizolid - avoid for at least 2 weeks after stopping linezolid and tedizolid.
Antidepressants: risk of hypertensive crisis with MAOIs and moclobemide - avoid for at least 2 weeks after stopping MAOIs.
Dopaminergics: avoid with rasagiline and selegiline

Metabolism

Hepatically metabolised.