Anxiogenic and proconvulsant effect of gatifloxacin in mice Nidhi Bharal, Sparsh Gupta, Sonam Khurana, Pramod Kumari Mediratta ⁎ , Krishna Kishore Sharma Department of Pharmacology, University College of Medical Sciences and G.T.B. Hospital, Delhi-110095, India Received 9 March 2007; received in revised form 10 October 2007; accepted 18 October 2007 Available online 25 October 2007 Abstract The present study was performed to assess the neurological and neurobehavioural effects of gatifloxacin after its oral administration in two doses: 25 and 50 mg/kg for 7 days and 14 days in mice. The neurobehavioural parameters used for the short-term study (×7 days) were pentylenetetrazole-induced seizure, forced swim test, elevated plus-maze, spontaneous alternation behaviour and rota-rod tests. However, only pentylenetetrazole-induced seizure and rota-rod tests were performed in long term (×14 days) study. The results showed proconvulsant effect of gatifloxacin (50 mg/kg) in pentylenetetrazole-induced seizure test after both short- and long-term administration studies. Gatifloxacin in both doses showed an anxiogenic effect. However, in both doses, it did not show any effect on memory and mood as the drug did not show any effect in alternation behaviour and forced swim tests. In the long term study, gatifloxacin in 50 mg/kg, p.o. produced grip impairing effect only after 14 days of administration. These results reveal that gatifloxacin possesses proconvulsant and anxiogenic effects but it does not have an effect on mood and memory. Besides, long term administration of gatifloxacin for 14 days was found to reduce grip strength indicating its movement impairing effect in mice. © 2007 Elsevier B.V. All rights reserved. Keywords: Gatifloxacin; Neurological effects; Anxiety 1. Introduction Fluoroquinolones are one of the widely prescribed groups of antimicrobial drugs. Although these drugs have demonstrated low incidence of side effects, several reports indicate central nervous system (CNS) toxicity in the form of headache, dizziness, tiredness, nightmares, confusion, insomnia and anxiety in 1–7% of treated patients. Other studies have described severe hallucinations, agitation, restlessness, depres- sion and convulsions as manifestations of CNS toxicity of fluoroquinolones (Christ, 1990; Galatti et al., 2005; Thomas, 1994). However, convulsions appear to be the most severe adverse effect of fluoroquinolones in patients with underlying CNS disease and in patients who were concurrently treated either with certain nonsteroidal antiinflammatory agents or theophylline (De Sarro et al., 1997; Owens and Ambrose, 2005; Schmuck et al., 1998; Simpson and Brodie, 1985). The proconvulsant and epileptogenic effects have been observed with quinolones such as ciprofloxacin, ofloxacin, norfloxacin, pefloxacin and some newer agents, like levofloxacin, trova- floxacin and sparfloxacin in clinical as well as experimental studies (Akahane et al., 1993; Anastasio et al., 1988; Bharal et al., 2006; Janknegt, 1990; Lucent et al., 1988; Melvani and Speed, 2000; Rewari and Prabhu, 1999; Yamamoto et al., 1998). Certain quinolones like ciprofloxacin, gatifloxacin and pefloxacin have been found to cause psychosis in some patients receiving them (Hesslinger et al., 1996; Mulhall and Bergmann, 1995; Satyanarayana and Campbell, 2006; Reeves, 2007). Levofloxacin and sparfloxacin have been shown to possess anxiogenic potential in animal studies (Bharal et al., 2006; Erden et al., 2001). Fluoroquinolones have also been shown to be associated with tendinopathy and arthropathy in younger patients, receiving these agents (Khaliq and Zhanel 2003; Mc Ewan and Davey, 1988; Mc Garvey et al., 1996). The first case of tendon rupture by ciprofloxacin was reported in 1987 (Mc Ewan and Davey, 1988). There is experimental evidence suggesting movement impairing effects with sparfloxacin, fleroxacin, pefloxacin, lomefloxacin, levofloxacin, ofloxacin in rodents. (Bharal et al., 2006; Kashida and Kato, 1997). Available online at www.sciencedirect.com European Journal of Pharmacology 580 (2008) 130 – 134 www.elsevier.com/locate/ejphar ⁎ Corresponding author. Tel.: +91 11 22592972 75x5704. E-mail address: drpramod_k@yahoo.com (P.K. Mediratta). 0014-2999/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2007.10.035