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Novel α1-adrenoceptor antagonism by the fluroquinolone antibiotic trovafloxacin

James A Angus1, Christine E Wright1

  • 1Cardiovascular Therapeutics Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Victoria 3010, Australia.

European Journal of Pharmacology
|September 4, 2016
PubMed

Insights

Trovafloxacin, a fourth-generation fluoroquinolone antibiotic, acts as a weak competitive antagonist of alpha-1 adrenoceptors. This finding may explain previously observed central nervous system side effects during clinical use.

Area of Science:

  • Pharmacology
  • Vascular Biology
  • Medicinal Chemistry

Background:

  • Trovafloxacin, a fluoroquinolone antibiotic, inhibits pannexin-1 channels involved in ATP release.
  • Pannexin-1 channels play a role in alpha-1 adrenoceptor-mediated vasoconstriction.
  • Investigating trovafloxacin's interaction with alpha-1 adrenoceptors is of interest.

Purpose of the Study:

  • To investigate the potential of trovafloxacin as an alpha-1 adrenoceptor antagonist.
  • To determine the affinity and selectivity of trovafloxacin for alpha-1 adrenoceptors.

Main Methods:

  • Myography was used to assess concentration-response curves in rat mesenteric small arteries.
  • Methoxamine and phenylephrine were used as alpha-1 adrenoceptor agonists.
  • Trovafloxacin's effect was compared to prazosin and its effects on other receptor pathways were evaluated.

Main Results:

  • Trovafloxacin competitively antagonised methoxamine and phenylephrine concentration-response curves with pKB values of 5.54 and 5.32, respectively.
  • Trovafloxacin did not affect thromboxane mimetic (U46619) or endothelin-1 induced contractions.
  • The concentration range for trovafloxacin's activity was consistent across its antibiotic, pannexin-1 inhibitory, and alpha-1 adrenoceptor antagonist effects.

Conclusions:

  • Trovafloxacin is a weak competitive antagonist of alpha-1 adrenoceptors.
  • The observed central nervous system side effects of trovafloxacin, such as dizziness and headache, may be attributed to its alpha-1 adrenoceptor antagonism.
  • Trovafloxacin exhibits a similar concentration range for its diverse pharmacological activities.
Keywords:
Endothelin-1 (PubChem CID: 16132423)Methoxamine hydrochloride (PubChem CID: 6081)Pannexin-1 channelsPhenylephrine hydrochloride (PubChem CID: 5284443)PrazosinPrazosin hydrochloride (PubChem CID: 68546)PubChem CID: 16219283)TrovafloxacinTrovafloxacin mesylate (PubChem CID: 62960)U46619 (9,11-dideoxy-9α,11α-methanoepoxyprostaglandin F2αVascular contractionα(1)-adrenoceptors

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