Introduction and objective:
The aim of the study was to determine the effects of 3-(N-p-isopropoxyphenylsuccinimidomethylamino)-cinnamic acid (IPPSMA-CA – a new succinimide derivative) on the protective action of 4 classical antiepileptic drugs (AEDs): carbamazepine [CBZ], phenobarbital [PB], phenytoin [PHT] and valproate [VPA]), against maximal electroshock (MES)-induced tonic seizures in mice.

Material and Methods:
Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Acute adverse-effect profiles of the combination of IPPSMA-CA and 4 classical AEDs (CBZ, PB, PHT and VPA) with respect to motor performance, long-term memory and skeletal muscular strength were measured in the chimney, passive avoidance and grip-strength tests, respectively.

Results:
IPPSMA-CA administered at 150 mg/kg (i.p.) significantly elevated the threshold for electroconvulsions in mice (p<0.01). IPPSMA-CA at doses of 50 and 100 mg/kg, however, had no significant impact on the threshold for electroconvulsions in mice. Nor did IPPSMA-CA (100 mg/kg) significantly affect the anticonvulsant activity of CBZ, PB, PHT and VPA in the MES test in mice. None of the examined combinations of IPPSMA-CA (100 mg/kg, i.p.) with CBZ, PB, PHT and VPA (at their ED50 values from the MES-induced seizure test) affected motor coordination in the chimney test, long-term memory in the passive avoidance task, and muscular strength in the grip-strength test in mice. This indicates no possible acute adverse effects in animals.

Conclusions:
IPPSMA-CA elevated the threshold for electroconvulsions in mice in a dose-dependent manner. However, IPPSMA-CA at a sub-protective dose of 100 mg/kg did not affect the anticonvulsant action of various classical AEDs in the mouse MES model. Thus, the combinations of IPPSMA-CA with CBZ, PB, PHT and VPA are neutral from a preclinical viewpoint.