Anticonvulsant and acute adverse effect profiles of picolinic acid 2-fluoro-benzylamide in various experimental seizure models and chimney test in mice.
The objective of this study was to evaluate the anticonvulsant properties of picolinic acid 2-fluoro-benzylamide (Pic-2F-BZA) in numerous experimental seizure models [maximal electroshock (MES), bicuculline (BIC), pentylenetetrazole (PTZ), pilocarpine (PILO), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainic acid (KA) and N-methyl-D-aspartic acid (NMDA)-induced seizures]. Moreover, the acute adverse-effect profile of the agent with respect to impairment of motor performance was assessed in animals subjected to the chimney test. Results indicate that Pic-2F-BZA in time- and dose-dependent manners produced both the anti-electroshock action and acute adverse effects in the MES and chimney tests in mice respectively. The experimentally derived median effective dose (ED(50) value) in the MES test was 24.2 mg/kg (at 5 min after i.p. administration), whereas the median toxic dose (TD(50) value) in the chimney test was 71.7 mg/kg. Furthermore, Pic-2F-BZA produced clear-cut antiseizure effects in all chemically induced seizure models and its ED(50) values amounted to 19.9 mg/kg for KA-, 39.5 mg/kg for AMPA-, 56.2 mg/kg for PTZ-, 76.4 mg/kg for BIC-, 160.1 mg/kg for PILO- and 165.2 mg/kg for NMDA-induced seizures. Based on this study, one can conclude that Pic-2F-BZA, because of its broad spectrum of anticonvulsant action and the short time to peak of its maximum anticonvulsant effects (5 min after its i.p. administration), deserves more attention as a potential antiepileptic drug for status epilepticus patients.
Luszczki
Jarogniew J
JJ
Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, PL 20-090 Lublin, Poland. jluszczki@yahoo.com
Swiader
Mariusz J
MJ
Swiader
Katarzyna
K
Paruszewski
Ryszard
R
Turski
Waldemar A
WA
Czuczwar
Stanislaw J
SJ
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D001593:Benzyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009048:Motor Skills / Q000187:drug effects; D010848:Picolinic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy*
D000927:Anticonvulsants; D001593:Benzyl Compounds; D010848:Picolinic Acids