Articaine: Efficacy and Paresthesia in Dental Local Anesthesia A Peer-Reviewed Publication Written by J. Mel Hawkins, DDS, BScDAN, FADSA, DADBA, FICD, FPFA

This review analyzes the current reports and publications involving the performance and clinical effectiveness of local anesthetics (efficacy) and the rare occurrence of post-operative prolonged numbness or tissue hypersensitivity (paresthesia, dysesthesia). No particular local anesthetic is scientifically singled out as causing this effect. Historically, scientific data on superior performance of one local anesthetic compared to another was lacking. One recently published report, however, showed the statistically significant and superior effectiveness of articaine in obtaining anesthesia of first permanent molars by infiltration when compared to lidocaine. The paresthesia debate regarding the potential of a 4% local anesthetic solution to be allegedly more neurotoxic than other currently administered local anesthetic solutions of lesser concentrations is examined. There is a lack of conclusive and experimentally reproducible evidence, of the cause and effect of specific local anesthetics to chemically result in post-operative sequelae such as paresthesia. An examination of the potential causative factors associated with paresthesia suggests mechanical and/or neurotoxic phenomena. Further evidence and scientific study are required to conclusively determine the significant role, or lack thereof, of each factor. The Evolution of Articaine The synthesis of articaine (originally named carticaine) in 1969 created a new clinical and investigative enthusiasm in a market that had otherwise been dormant since the mid-1950s. Articaine was synthesized in Germany and then introduced for clinical use in Europe in 1976 (Ultracaine®, Hoechst Pharmaceuticals) and in Canada in 1982.1 It was reported to have superb diffusion capabilities, adequate duration (with the inclusion of a vasoconstrictor) and a very effective performance. A thiophene ring replaced the aniline ring on the lipophilic section of the molecule and, for the first time in local anesthetics, a sulfur atom was added within that thiophene structure. Initially, these new chemical entities invited careful scrutiny, even skepticism and criticism among researchers and clinicians. It took more than five years for the Food and Drug Administration (FDA) to approve this product for therapeutic use in the USA, and then, only in the 1:100,000 epinephrine concentration. This was in spite of the fact that the 1:200,000 epinephrine concentration had been available in Europe and Canada since 1976 and 1982, respectively (Septocaine®, Septodont Inc., April 2000). Final approval for the 1:200,000 compound was received in June 2006 for the United States. Since the mid-1970s, studies worldwide have repeatedly shown that the safety and efficacy of this “new” drug meet or surpass all assessment criteria.1 Classification Articaine is classified as an amide, similar to all other local anesthetics currently used in dentistry. Amides have superseded esters because of their enhanced performance. When measured against the ester forerunner procaine, the amides display a faster onset (the pKa is closer to physiological pH), reliably good clinical duration, and minimal local or systemic side effects.1,2,3 Allergic reactions are extremely rare with the amides, including articaine. The allergen paraminobenzoic acid (PABA), a frequent metabolite of ester metabolism, is not a byproduct of the hydrolysis phase of articaine.1,2 Chemistry and Pharmacokinetics of Articaine Articaine HCl is recognized by the chemical name 4-methyl-3 (2-[propylamino] propionamido)-2-thiophenecarboxilic acid, methyl ester hydrochloride.2 This chemical displays the following properties and behavior: 1. An amide group local anesthetic 2. A highly lipid-soluble thiophene aromatic ring 3. An ester hydrolysis component (90%) that contributes to the drug’s rapid metabolism Figure 1. Structural formula and physico-chemical data for articaine.