SYM 2206 (a potent non-competitive AMPA receptor antagonist) elevates the threshold for maximal electroshock-induced seizures ..
Curr Issues Pharm Med Sci., Vol.27, No.2, Pages 80-83
Jarogniew J. Luszczki1,2, Magdalena Leszkowicz1, Maria W. Kondrat-Wrobel1, Magdalena Florek-Luszczki3
1 Department of Pathophysiology, Medical University of Lublin, Ceramiczna 1, 20-150 Lublin, Poland
2 Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland
3 Department of Public Health, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland
SYM 2206 (a potent non-competitive AMPA receptor antagonist) elevates the threshold for maximal electroshock-induced seizures in mice
The aim of this study was to determine the effect of SYM 2206 (a potent non-competitive AMPA receptor antagonist) on the threshold for maximal electroshock (MEST)-induced seizures in mice. Electro-convulsions were produced in mice by means of a current (sine-wave, 50 Hz, maximum 500 V, strength from 4 to 14 mA, 0.2-s stimulus duration, tonic hind limb extension taken as the endpoint) delivered via ear-clip electrodes. SYM 2206 administered systemically (i.p.), 30 min before the MEST test, at doses of 2.5 and 5 mg/kg, did not alter the threshold for maximal electroconvulsions in mice. In contrast, SYM 2206 at doses of 10 and 20 mg/kg significantly elevated the threshold for maximal electro-convulsions in mice (P<0.01 and P<0.001). Linear regression analysis of SYM 2206 doses and their corresponding threshold increases allowed for the determination of threshold increasing doses by 20% and 50% (TID20 and TID50 values) that elevate the threshold in drug-treated animals over the threshold in control animals. The experimentally derived TID20 and TID50 values for SYM 2206 were 4.25 and 10.56 mg/kg, respectively. SYM 2206 dose-dependently increased the threshold for MEST-induced seizures, suggesting the anticonvulsant action of the compound in this seizure model in mice.
SYM 2206, threshold for maximal electroshock-induced seizures, TID20, TID50, mice
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