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Biological Chemistry

What's that stuff? Dental Anesthetics

Nonaddictive derivatives of cocaine numb the pain of dental work

by Elizabeth K. Wilson
June 29, 2009 | A version of this story appeared in Volume 87, Issue 26

Credit: Shutterstock
Credit: Shutterstock

As my dentist loomed above me with a gigantic syringe full of anesthetic, it didn’t seem like the right time to ask what precisely he was injecting into my gums.

But that last trip to the dentist for a routine filling turned into a protracted horror because my tooth refused to go numb. Several aborted drilling attempts and seven shots of anesthetic later, I was finally numb enough to withstand the procedure, but not woozy enough from the experience to forget my question.

I was dimly aware that the long-standing, popular word Novocaine is basically a catchall term—like Kleenex or Jell-O—for dental anesthetic. But surely modern dental anesthetics are exotic compounds discovered by using high-throughput technology and the like.

Nope. My dentist, Dr. Scott Levine, who has practiced in Berkeley, Calif., for more than 10 years, filled me in. “Very little has changed since I’ve been around,” he said. A handful of related, very effective compounds continue to be the anesthetic mainstays of any dental practice, varying mostly in terms of how quickly they take effect and how quickly they wear off.

With names like benzocaine, lidocaine, arti­caine, and mepivacaine, it’s easy to guess that they’re all derivatives of the original naturally occurring local anesthetic, cocaine.

The analgesic properties of cocaine, an alkaloid found in coca leaves, have been known for centuries. It didn’t take long after cocaine was isolated in the 1800s for chemists to begin searching for less addictive alternatives for use as a local anesthetic.

The first such alternative was Novocaine, the trade name given to the compound procaine. Synthesized in the late 1800s, procaine could be injected, and patients couldn’t get hooked. For decades, it reigned as the archetypal dental anesthetic.

Procaine and “caine” successor molecules are amino compounds with a similar framework: a hydrophilic amine and a lipophilic aromatic group, connected by either an ester- or an amide-based linkage, explains Matthias C. Lu, a professor of medicinal chemistry and pharmacognosy at the University of Illinois, Chicago, and anesthetic chemistry expert. Long ago, these two classes were given the names “amino ester” and “amino amides,” and those labels have stuck, Lu says.

There’s some controversy over the molecules’ anesthetic mechanism. Lu has proposed that the molecules bind and interact with a specific receptor on the nerve cell membrane. Other pharmacologists believe that the molecules merely disturb the membrane structure and thus the receptor, albeit indirectly. In either case, though, the result is that the flows of sodium ions into and potassium ions out of the cells are blocked, preventing a biochemical chain reaction that causes the cells to fire pain signals to the brain.

The amino ester class of anesthetics, which includes procaine, has shortcomings, however, including instability and a higher risk of inducing an allergic reaction—likely because the enzyme pseudocholinesterase converts them into para-aminobenzoic acid, an immune system activator. All anesthetics also pose a slight risk of cardiac arrest.

In the 1940s, chemists synthesized the first amino amide anesthetic, lidocaine (Xylocaine), which didn’t carry the same allergic risk as the ester amides and lasted longer than procaine. Consequently, ester amides have largely fallen out of use.

Benzocaine is one amino ester that’s still a dental mainstay, but as a topical anesthetic. It’s in the goo the dentist uses to numb your gum before injecting anesthetic, and it is the same stuff that’s in over-the-counter anesthetic products such as the oral ulcer treatment Orajel.

New variants of amino amides, such as articaine and mepivacaine, have proliferated. Most injectable dental anesthetics also include a minute amount of epinephrine (1 part per 100,000), which constricts blood vessels, preventing the injected anesthetic from spreading out into the body quickly.

For now, most research on local anesthetics focuses on decreasing toxicity—as in the case of the relatively new levobupivacaine, which has fewer cardiac side effects than other anesthetics. But if Lu’s proposed mechanism is accurate, then an entirely new generation of anesthetics, with molecular linkages to enhance the binding of the molecules to the nerve cells, could be envisioned.

Even so, the local anesthetics now available clearly work well, so why didn’t my stubborn tooth go numb? The occasional resistance to numbing isn’t indicative of the effectiveness of the anesthetics but of the position of nerve endings in different patients, Levine explains. What did the trick for me was a booster shot right at the base of the tooth.

Armed with all of this knowledge about anesthetics, I’d still prefer to avoid situations that require them. That’s why I’m focusing on a less invasive dental procedure: flossing.



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