Cocaine was widely used as a local anesthetic after Carl Koller (1857-1944) demonstrated its effectiveness in 1884. By the end of the 1800s, however, the addictive properties of cocaine had been recognized. Doctors, realizing they needed to develop substitutes for cocaine's active anesthetic ingredient, carefully studied the drug's exact chemical structure. Many of the initial synthetic cocaine products that were developed were too irritating to be of any practical use. The first successful substitute was Ernest Fourneau's (1872-1949) stovaine, discovered in 1904.

Fourneau's product was soon followed, in 1905, by procaine, the discovery of German Alfred Einhorn. Einhorn gave his substance the trade name Novocain, from the Latin novus ("new") plus cocaine. Introduced by Heinrich Braun (1862-1934) in 1905, novocain soon showed that it had all the positive effects of cocaine with none of that drug's drawbacks. Guido Fisher popularized Novocain, or procaine, in the United States. Injected by needle, Novocain immediately became popular as a local anesthetic for both medical and dental purposes.

Other similar synthetic substitutes for cocaine produced after novocain include tropocaine, aucaine, monocaine, and lignocaine.