Clinical Uses of the Tetracyclines

Abstract

The first tetracycline to be discovered, chlortetracycline, was isolated from Streptomyces aurefaciens in 1944. Since 1944, several tetracycline analogues have been developed including oxytetracycline, which was introduced in 1950, tetracycline hydrochloride in 1953, and demethylchlortetracycline (demeclocycline). In the late 1950s it was discovered that the 6-hydroxyl group could be removed from the basic tetracycline group, which resulted in the 6-deoxytetracyclines, with significantly different microbiological and pharmacokinetic properties. In the 1960s the so-called “second generation” or long-acting tetracyclines were introduced. Doxycycline was isolated in 1962 (Schach von Wittenau et al. 1962) and minocycline was introduced in 1967 (Redin 1967). Although all tetracyclines inhibit bacterial protein synthesis, there are significant differences in inherent antibacterial activity between the short-acting and long-acting tetracyclines.