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Anticonvulsant and acute adverse effect profiles of picolinic acid 2‐fluoro‐benzylamide in various experimental seizure models and chimney test in mice
Author(s) -
Luszczki Jarogniew J.,
Swiader Mariusz J.,
Swiader Katarzyna,
Paruszewski Ryszard,
Turski Waldemar A.,
Czuczwar Stanislaw J.
Publication year - 2008
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2007.00547.x
Subject(s) - anticonvulsant , kainic acid , pharmacology , chemistry , ampa receptor , bicuculline , medicine , anesthesia , glutamate receptor , epilepsy , biochemistry , antagonist , receptor , psychiatry
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), α‐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.