Prilocaine

Prilocaine (/ˈpraɪləˌkeɪn/^[1]) is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Löfgren. In its injectable form (trade name Citanest), it is often used in dentistry. It is also often combined with lidocaine as a topical preparation for dermal anesthesia (lidocaine/prilocaine or EMLA), for treatment of conditions like paresthesia. As it has low cardiac toxicity, it is commonly used for intravenous regional anaesthesia (IVRA).

Prilocaine

Clinical data
Trade names	Citanest
AHFS/Drugs.com	Monograph
MedlinePlus	a603026
License data	EU EMA: by INN US DailyMed: Prilocaine
Pregnancy category	AU: A
Routes of administration	Subcutaneous
ATC code	N01BB04 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) US: ℞-only
Pharmacokinetic data
Protein binding	55%
Metabolism	Liver and kidney
Elimination half-life	10-150 minutes, longer with impaired liver or kidney function
Identifiers
IUPAC name (RS)-N-(2-methylphenyl)-N2-propylalaninamide
CAS Number	721-50-6 Y
PubChem CID	4906
IUPHAR/BPS	7276
DrugBank	DB00750 Y
ChemSpider	4737 Y
UNII	046O35D44R
KEGG	D00553 Y as HCl: D01243 Y
ChEBI	CHEBI:8404 Y
ChEMBL	ChEMBL1194 Y
CompTox Dashboard (EPA)	DTXSID7031955
ECHA InfoCard	100.010.871
Chemical and physical data
Formula	C13H20N2O
Molar mass	220.316 g·mol−1
3D model (JSmol)	Interactive image
Chirality	Racemic mixture
Melting point	37 to 38 °C (99 to 100 °F)
SMILES O=C(Nc1ccccc1C)C(NCCC)C
InChI InChI=1S/C13H20N2O/c1-4-9-14-11(3)13(16)15-12-8-6-5-7-10(12)2/h5-8,11,14H,4,9H2,1-3H3,(H,15,16) Y Key:MVFGUOIZUNYYSO-UHFFFAOYSA-N Y
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Contraindications

In some patients, ortho-toluidine, a metabolite of prilocaine, may cause methemoglobinemia, which may be treated with methylene blue. Prilocaine may also be contraindicated in people with sickle cell anemia, anemia, or symptomatic hypoxia.^[2]

Combinations

It is given as a combination with the vasoconstrictor epinephrine under the trade name Citanest Forte. It is used as a eutectic mixture with lidocaine, 50% w/w, as lidocaine/prilocaine. The mixture is an oil with a melting point of 18 °C (64 °F). A 5% emulsion preparation, containing 2.5% each of lidocaine/prilocaine, is marketed by APP Pharmaceuticals under the trade name EMLA (an abbreviation for eutectic mixture of local anesthetics).^[3]

Compendial status

• United States Pharmacopeia 31 ^[4]

Synthesis

Synthesis:^[5] Patents:^[6][7] Revised:^[8] Sino:^[9]

The amidation between o-toluidine [95-53-4] (1) and 2-bromopropionyl bromide [563-76-8] (2) leads to 2-bromo-N-(2-methylphenyl)propanamide [19397-79-6] (3). Displacement of the remaining halide with propylamine [107-10-8] (4) completed the synthesis of prilocaine (5).

See also

• Lidocaine/prilocaine

References

1. "Prilocaine". Merriam-Webster.com Dictionary. Merriam-Webster. Retrieved 2016-01-21.
2. Patel V, Morrissey J (2011-09-15). Practical and Professional Clinical Skills. Oxford University Press. p. 267. ISBN 9780199585618.
3. "Topical Anesthesia Use in Children: Eutectic Mixture of Local Anesthetics". Medscape.com. Retrieved 2014-01-07.
4. The United States Pharmacopeial Convention, Revision Bulletin: Lidocaine and Prilocaine Cream–Revision to Related Compounds Test, archived from the original on 5 July 2010, retrieved 10 July 2009
5. Löfgren, Nils; Tegnér, Claës; Arwidsson, Barbro; Varde, E.; Westin, Gertrud (1960). "Studies on Local Anesthetics. XX. Synthesis of Some alpha-Monoalkylamino-2-methylpropionanilides. A New Useful Local Anesthetic.". Acta Chemica Scandinavica 14: 486–490. doi:10.3891/acta.chem.scand.14-0486.
6. Anon., GB 839943 (to Astra Apotekarnes Kem Fab).
7. Lofgren Nils Magnus, Tegner Claes Philip, U.S. patent 3,160,662 (1964 to Astra Apotekarnes Kem Fab).
8. Demare, Patricia; Regla, Ignacio (2012). "Synthesis of Two Local Anesthetics from Toluene: An Organic Multistep Synthesis in a Project-Oriented Laboratory Course". Journal of Chemical Education. 89 (1): 147–149. doi:10.1021/ed100838a.
9. 沈文晖, 杨忠鑫, 葛小强, 张宇生, 邹玉龙, 张强, 杨继斌, 蔡中文, CN 105439887 (2016 to 重庆康乐制药有限公司).

External links

• "Prilocaine". Drug Information Portal. U.S. National Library of Medicine.
• "Prilocaine hydrochloride". Drug Information Portal. U.S. National Library of Medicine.