Assessment of the anticonvulsant potency of various benzylamide derivatives in the mouse maximal electroshock-induced seizure threshold model

Purpose the aim of this study was to assess the anticonvulsant potency of 6 various benzylamide derivatives [i.e.,nicotinic acid benzylamide (nic-bza),picolinic acid 2-fluoro-benzylamide (2f-pic-bza),picolinic acid benzylamide (pic-bza),(rs)-methyl-alanine-benzylamide (me-ala-bza),isonicotinic acid benzylamide (iso-nic-bza),and (r)-n-methyl-proline-benzylamide (me-pro-bza)] in the threshold for maximal electroshock (mest)-induced seizures in mice. methods electroconvulsions (seizure activity) were produced in mice by means of a current (sine-wave,50 hz,500 v,strength from 4 to 18 ma,ear-clip electrodes,0.2-s stimulus duration,tonic hindlimb extension taken as the endpoint). results nic-bza,2f-pic-bza,pic-bza,me-ala-bza,iso-nic-bza,and me-pro-bza administered systemically (ip) in a dose-dependent manner increase the threshold for maximal electroconvulsions in mice. linear regression analysis of nic-bza,2f-pic-bza,pic-bza,meala-bza,isonic-bza,and me-pro-bza doses and their corresponding threshold increases allowed determining threshold increasing doses by 20% (tid20 values) that elevate the threshold in drug-treated animals over the threshold in control animals. the experimentally derived tid20 values in the mest test for nic-bza,2f-pic-bza,pic-bza,me-ala-bza,iso-nic-bza,and me-pro-bza were 7.45 mg/kg,7.72 mg/kg,8.74 mg/kg,15.11 mg/kg,21.95 mg/kg and 28.06 mg/kg,respectively. conclusion the studied benzylamide derivatives can be arranged with respect to their anticonvulsant potency in the mest test as follows: nic-bza > 2f-pic-bza > pic-bza > me-ala-bza > iso-nic-bza > me-pro-bza. © 2015 institute of pharmacology,polish academy of sciences. published by elsevier sp. z o.o. all rights reserved.