RESEARCH MONOGRAPH · KDC-MN-1313
Prilocaine
Prilocaine (Citanest) is an amide local anesthetic with the lowest systemic toxicity in the class, reflecting rapid hepatic clearance and high tissue redistribution. It is the partner of lidocaine in EMLA cream, where the eutectic mixture of the two oils provides effective topical anesthesia of intact skin for venipuncture and minor procedures. The defining downside: dose-dependent methemoglobinemia. Liver enzymes hydrolyze prilocaine to o-toluidine, which is hydroxylated to a metabolite that oxidizes hemoglobin iron and prevents oxygen binding. Cumulative exposure can produce clinically significant methemoglobinemia requiring methylene blue therapy. Risk amplifies in G6PD deficiency, NADH-methemoglobin reductase deficiency, or with concurrent oxidant drugs. Widely used in European and Asian dental cartridges. Not stocked by Kodiac. This monograph is provided for research and educational reference.
Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.
Amide local anesthetic (intermediate-acting, low-toxicity)
An amide local anesthetic with the lowest systemic toxicity in the class but the dose-dependent risk of methemoglobinemia from o-toluidine metabolite generation.
Abstract
Prilocaine (N-(2-methylphenyl)-2-(propylamino)propanamide; CAS 721-50-6; molecular formula C13H20N2O; molecular weight 220.31) is an amide local anesthetic developed at AB Astra in the late 1950s and introduced clinically in the 1960s (Citanest). The compound has the lowest systemic toxicity in the amide class (CNS and cardiac toxic thresholds higher than lidocaine, mepivacaine, or bupivacaine), reflecting rapid hepatic clearance and high tissue redistribution. Prilocaine is the principal component of the EMLA cream alongside lidocaine, where the eutectic mixture of the two oils provides effective topical anesthesia of intact skin for venipuncture and minor superficial procedures. The principal clinical limitation is dose-dependent methemoglobinemia: prilocaine is hydrolyzed in the liver to o-toluidine, which is hydroxylated to a methemoglobin-generating metabolite, producing clinically significant methemoglobinemia that may require methylene blue therapy. The risk is amplified in patients with G6PD deficiency, NADH-methemoglobin reductase deficiency, or concurrent administration of other oxidant drugs (dapsone, sulfamethoxazole, benzocaine). Mechanism is the standard amide voltage-gated sodium channel block. Onset and duration are intermediate (similar to lidocaine and mepivacaine). Prilocaine is widely used in dental anesthesia in Europe and Asia and is the principal component of dental cartridges in several markets.
Mechanism of action
Voltage-gated sodium channel block. Hepatic hydrolysis to o-toluidine drives the methemoglobinemia risk.
Reported research dose ranges
Reported research dose ranges vary across the published literature.
References
- Hjelm M, Holmdahl MH. Methaemoglobinaemia induced by prilocaine. Acta Anaesthesiol Scand 1965.
- Vasters FG, et al. Risk factors for postoperative methaemoglobinaemia after regional anaesthesia. Acta Anaesthesiol Scand 2006.
- Buckley MM, Benfield P. Eutectic lidocaine/prilocaine cream. Drugs 1993.
Read the full monograph
Available as a research-use-only PDF download.
The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.
FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.