Relationship Between Fluoroquinolone Structure and Neurotoxicity Revealed by Zebrafish Neurobehavior

Central nervous system side effects are one of the most frequently reported adverse reactions of fluoroquinolones (FQs). However, the mechanism is not fully understood. In this study, zebrafish (Danio rerio) were used as a model system. We quantified neurobehavior by recording indicators with automated video-tracking and used liquid chromatography-tandem mass spectrometry to detect drug absorption in vivo. We studied embryotoxicity and effects on zebrafish locomotor activity of 17 typical FQs. In addition, we calculated the stable conformation of typical FQs in aqueous conditions. The relationships between structure, neurotoxicity, and embryotoxicity were analyzed. The results indicate: (1) The effects of FQs on zebrafish neurobehavior can be divided into four categories. Type I has no significant influence on locomotor activity. Type II suppresses locomotor activity. Type III inhibits at low concentration and stimulates at high concentration. Type IV stimulates and then suppresses (biphasic response). (2...