Trovafloxacin – an antibiotic with additional properties
The axiom of pharmacology is that every drug has more than one action. The art and skill of therapeutics is to know the dose range wherein the drug may be selective for one particular action. Trovafloxacin is a broad spectrum fluroquinolone antibiotic that was withdrawn from use in 1999 because of rare hepatic toxicity. Recently it was found to inhibit pannexin-1 channel opening in apoptotic Jurkat cells (human immortalised T-lymphocytes). This additional property of trovafloxacin was found through a screen of a small molecule library of 1280 compounds. Given our interest in pannexin-1 channels in α1-adrenoceptor-mediated contraction of small arteries, we tested trovafloxacin against methoxamine, phenylephrine, U46619 and endothelin-1. To our surprise trovafloxacin was a competitive antagonist against methoxamine (pKB 5.5) and phenylephrine (pKB 5.3), but not against U46619 or endothelin-1. Interestingly, trovafloxacin was similarly potent against Jurkat cell pannexin channels, a1-adrenoceptors and its concentration range as an antibiotic. In comparison, with prazosin (pKB 9.8), trovafloxacin was a weak α1-adrenoceptor antagonist, but this action may well explain its common clinical side effects of dizziness, flushing and headache reported in clinical trials. The molecular structures of trovafloxacin and prazosin share a quinolone moiety. In conclusion, trovafloxacin has at least 3 pharmacological properties at the same concentration, again illustrating the importance of using a range of assays to classify the actions of therapeutic drugs.
Associate Professor Christine E. Wright, BSc Hons, PhD, Laboratory Head
Mr Mark Ross-Smith, BSc Hons, Senior Research Assistant
- Angus JA, Wright CE. Novel α1-adrenoceptor antagonism by the fluroquinolone antibiotic trovafloxacin. Eur J Pharmacol 2016; 791: 179-184.
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