Anxiolytic and anticonvulsant effect of Ibuprofen derivative through GABAergic neuromodulation in adult Zebrafish

Abstract

Anxiety and epilepsy affect millions of people worldwide, and the treatment of these pathologies involves the use of Benzodiazepines, drugs that have serious adverse effects such as dependence and sedation, so the discovery of new anxiolytic and antiepileptic drugs are necessary. Many routes for synthesizing ibuprofen derivatives have been developed, and these derivatives have shown promising pharmacological effects. Therefore, this study aims to evaluate its anxiolytic and anticonvulsant effect against the adult Zebrafish animal model of Ibuprofen (IBUACT) and its interaction with the GABAergic receptor through in silico studies. The light/dark preference test (Scototaxis test) was used to evaluate the anxiolytic behavior of adult Zebrafish acutely treated with IBUACT and Diazepam, and their anticonvulsant effects were investigated through the pentylenetetrazol (PTZ)-induced seizure model. Animals treated with IBUACT showed anxiolytic behavior similar to Diazepam, and pretreatment with flumazenil reversed this behavior. PTZ-induced seizures were delayed by IBUACT in all three stages and were shown to bind strongly in the Diazepam region of GABA_A. In addition, this work presents evidence of new pharmacological applications of ibuprofen derivative in pathologies of the central nervous system (CNS), opening the horizon for new studies.

Communicated by Ramaswamy H. Sarma

Keywords:

• Anxiety
• convulsion
• Zebrafish

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We thank the financial support from CNPq, CAPES, and FUNCAP. Hélcio S. Santos acknowledges financial support from the PQ/BPI-FUNCAP (Grant BP4-0172-00075.01.00/20), Alexandre M.R. Teixeira acknowledges financial support from CNPq (Grant 305719/2018-1).