title: Anticonvulsant and acute neurotoxic characteristics of nicotinic acid benzylamide: a preclinical study.
abstract: The aim of this study was to evaluate time-course and dose-response relationships of nicotinic acid benzylamide (Nic-BZA) with regard to its anticonvulsant activity in the maximal electroshock (MES)-induced seizures and acute neurotoxic effects in terms of motor coordination impairment in the chimney test in mice. The experimental determination of both median effective dose (ED(50)) and median toxic dose (TD(50)) allowed for the calculation of protective index (PI) values characterizing a preclinical profile of Nic-BZA. Results indicated that Nic-BZA produced the time-dependent and clear-cut anticonvulsant activity in the MES test and its ED(50) values ranged between 35.7 and 84.0 mg/kg (after the ip administration of the agent at 5 and 60 min, respectively), and between 72.0 and 152.1 mg/kg (at 5 and 60 min, respectively, following the po administration of Nic-BZA). In the chimney test, the TD(50) values for Nic-BZA, after its ip administration ranged between 188.5 and 509.9 mg/kg, whereas following its po administration the TD(50) values for Nic-BZA were between 552 and 1222.1 mg/kg. The PI values for Nic-BZA, calculated at various times after its ip and po administrations (ranging between 3.56 and 17), revealed that the agent has a favorable profile, when considering its both anticonvulsant and acute neurotoxic effects in this preclinical study. Based on this study, one can conclude that Nic-BZA might occur advantageous as a potential antiepileptic drug for breaking seizure attacks in patients with epilepsy.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Medical University, Jaczewskiego 8, PL 20-090 Lublin, Poland. mariusz.swiader@am.lublin.pl
authors.forename: Mariusz J
authors.initials: MJ
authors.lastname: Swiader
authors.forename: Jarogniew J
authors.initials: JJ
authors.lastname: Łuszczki
authors.forename: Ryszard
authors.initials: R
authors.lastname: Paruszewski
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Czuczwar
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Turski
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009498:Neurotoxins / Q000494:pharmacology*; D009525:Niacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D001593:Benzyl Compounds; D009498:Neurotoxins; C484800:nicotinic acid benzylamide; D009525:Niacin