Protective action of nicotinic acid benzylamide in a variety of chemically-induced seizures in mice

Abstract

Purpose: The study aims to assess the anticonvulsant effects offered by benzylamide nicotinic acid (Nic-BZA) in many animal models of chemically-induced seizures (i.e., pentylenetetrazole [PTZ], pilocarpine [PILO], bicuculline [BIC], α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA], kainic acid [KA], and N-methyl-d-aspartic acid [NMDA]). Additionally, it analyses side effects of administering Nic-BZA in the form of loss of co-ordination and memory impairment as evaluated in the rotarod and passive avoidance tests, respectively.

Results: Antiseizure activity of Nic-BZA was reported in numerous models of chemically-induced seizures and its ED50 value was 37.1mg/kg for PTZ, 53.0mg/kg for AMPA, 81.4mg/kg for BIC, 86.3mg/kg for KA, and 182.6mg/kg for PILO. Moreover, Nic-BZA was totally ineffective (in dosages of up to 200mg/kg) in mice challenged with NMDA-induced seizures. The evaluation of the side effects present shortly after dosing in the rotarod test has revealed neurotoxicity of Nic-BZA with experimentally determined TD50 value of 188.5mg/kg. Protective index (PI) assessment analysis for Nic-BZA has disclosed a substantial difference between the dosage resulting in acute impairment of co-ordination and the dosage resulting in anticonvulsant effect in various chemically evoked seizures, remaining practically ineffective (in dosages of up to 200mg/kg) in mice subjected to the NMDA-induced seizure test. Additionally, Nic-BZA (in dosages of up to 100mg/kg) did not impair long-term memory in mice.

Conclusions: Summing up, Nic-BZA has a wide anticonvulsant effect in different experimental epilepsy models.

Keywords: Chemically induced seizures; Nicotinic acid benzylamide; Passive avoidance task; Protective index; Rotarod test.