title: Assessment of the anticonvulsant potency of various benzylamide derivatives in the mouse maximal electroshock-induced seizure threshold model.
abstract: OBJECTIVE
  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, 50Hz, 500V, strength from 4 to 18mA, 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 7.45mg/kg, 7.72mg/kg, 8.74mg/kg, 15.11mg/kg, 21.95mg/kg and 28.06mg/kg, respectively.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Lublin, Poland. Electronic address: mariusz.swiader@umlub.pl.
authors.forename: Mariusz J
authors.initials: MJ
authors.lastname: Świąder
authors.affiliation: Department of Drug Chemistry, Medical University of Warsaw, Warszawa, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Paruszewski
authors.affiliation: Department of Pathophysiology, Medical University of Lublin, Lublin, Poland; Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland.
authors.forename: Jarogniew J
authors.initials: JJ
authors.lastname: Łuszczki
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D001596:Benzylamines / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000379:methods; D008297:Male; D051379:Mice; D012640:Seizures / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D001596:Benzylamines; C030796:benzylamine
keywords: Benzylamide derivatives; Threshold for maximal electroshock-induced seizures; Threshold increasing dose by 20%