Definition
ChEBI: An amino acid amide in which N-propyl-DL-alanine and 2-methylaniline have combined to form the amide bond; used as a local anaesthetic.
Brand name
lidocaine/prilocaine topical
Brand names: Emla, LiproZonePak, Dolotranz, Livixil Pak, and Anodyne LPT.
General Description
Prilocaine hydrochloride is a water-soluble salt available asa solution for nerve block or infiltration in dental procedures.Prilocaine is used for intravenous regional anesthesiaas the risk of CNS toxicity is low because of the quick metabolism.Prilocaine prepared in the crystal form is used inEMLA for topical administration to decrease painful needlesticks in children. Prilocaine 4% solution should be protectedfrom light and the manufacturer recommends discardingif the solution turns pinkish or slightly darker than lightyellow. Solutions are available in various concentrations upto 4%, with or without epinephrine and with or withoutpreservatives.
Pharmacology
Prilocaine is less toxic than lidocaine, with a high clearance, attributable to
metabolism in the lungs, kidneys and liver. It is associated with
methaemoglobinaemia at doses >600mg. It is sometimes used at a
concentration of 0.5% for the provision of intravenous regional anaesthesia, and a combination of prilocaine 3% with felypressin is
available for low-volume local infiltration anaesthesia in dental surgery. A
2% formulation is also available for spinal anaesthesia. Prilocaine is also
formulated in a eutectic mixture with lidocaine (EMLA) for topical
anaesthesia.
Clinical Use
Prilocaine metabolism has beenstudied extensively in animal models, less is known aboutthe human metabolites or the human CYP enzymes involvedin their formation . The metabolism of prilocainein the liver yields o-toluidine, which is a possiblecarcinogen. Many aromatic amines, including o-toluidinehave been shown to be mutagenic, and metabolites of otoluidinehave been shown to form DNA adducts.Metabolites of o-toluidine are also believed to be responsiblefor the methemoglobinemia observed with prilocaineuse. To decrease the potential for methemoglobinemia, strictadherence to the maximum recommended dose should befollowed. Metabolism of prilocaine is extensive with lessthan 5% of a dose excreted unchanged in the urine.
Synthesis
Prilocaine, 2-(propylamino)-o-propiontoluidine (2.2.14), is structurally
related to the exact same group as ethidocaine, yet it differs structurally in that during synthesis, o-toluidine is used instead of 2,6-dimethylaniline, and instead of a butyric acid, a
fragment of propionic acid, and a terminal propylethylamine group is replaced with a
propylamine group. In order to synthesize prilocaine, o-toluidine is reacted with bromopropionyl bromide, and the resulting bromopropionyltoluidide (2.2.13) is then reacted
with propylamine, which gives prilocaine [22,23].
