Trimethoprim is a synthetic antibiotic that inhibits dihydrofolate reductase (DHFR) which is necessary for the synthesis of purines, amino acids, and thymidylic acid, with prominent selectivity for bacterial DHFR over mammalianDHFR (IC50s = 5 and 30,000 nM, respectively). Trimethoprim is used mainly in the prophylaxis and treatment of urinary tract infections.
Trimethoprim (TMP), an inhibitor of dihydrofolate reductase, decreases the level of tetrahydrofolate supplying one-carbon units for biosynthesis of nucleotides, proteins, and panthotenate. TMP caused induction of DnaK, DnaJ, GroEL, ClpB, and IbpA/B Hsps[3]. Trimethoprim exerts antimicrobial activity by blocking the reduction of dihydrofolate to tetrahydrofolate, the active form of folic acid, by susceptible organisms. It has inhibitory activity for most gram-positive aerobic cocci and some gram-negative aerobic bacilli. Trimethoprim constitutes very effective therapy for women with acute symptomatic urinary tract infections caused by E. coli[4]. The antimicrobial combination of trimethoprim and sulfamethoxazole is active in vitro against a variety of gram-positive and gram-negative bacteria[5]. At the dosages used, trimethoprim has generally been well tolerated and in studies comparing it with co-trimoxazole overall, skin rashes and gastrointestinal upset have occurred less frequently with trimethoprim than with co-trimoxazole[6].
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