title: Protective action of nicotinic acid benzylamide in a variety of chemically-induced seizures in mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland. Electronic address: mariusz.swiader@am.lublin.pl.
authors.forename: Mariusz J
authors.initials: MJ
authors.lastname: Świąder
authors.affiliation: Department of Pathophysiology, Medical University, Lublin, Poland; Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland.
authors.forename: Jarogniew J
authors.initials: JJ
authors.lastname: Łuszczki
authors.affiliation: Department of Drug Chemistry, Medical University, Warszawa, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Paruszewski
authors.affiliation: Department of Applied Pharmacy, Medical University, Lublin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Świąder
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland.
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Turski
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001593:Benzyl Compounds / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy; D057567:Memory, Long-Term / Q000187:drug effects; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009525:Niacin / Q000031:analogs & derivatives* / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D001593:Benzyl Compounds; D020011:Protective Agents; C484800:nicotinic acid benzylamide; D009525:Niacin; D016202:N-Methylaspartate
keywords: Chemically induced seizures; Nicotinic acid benzylamide; Passive avoidance task; Protective index; Rotarod test