ABSTRACT
Trimethoprim (TMP), or 2,4-diamino-5-(3,4,5-trimethoxybenzyl)-pyrimidine, was synthesized in 1956 by Hitchings at the Wellcome Laboratories in the USA (Roth et al., 1962). It has both antibacterial and antimalarial activity, whereas another diaminopyrimidine, pyrimethamine, which was synthesized in 1951 (Russell and Hitchings, 1951), is mainly active against malaria and Toxoplasma gondii (see Chapter 93, Pyrimethamine). TMP interrupts the bacterial purine synthesis and folate synthesis pathway, acting in the same metabolic pathway as the sulfonamides. The combination of these two drugs, therefore, has a synergistic effect against certain bacteria (Bushby and Hitchings, 1968; Darrell et al., 1968).
