The antiseizure activities of hydrazine carboximidamide derivatives in rat: behavioral and electrophysiological studies

Despite of dramatic achievement in discovery of new chemical entities as antiepileptic drugs (AEDs), about one-third of patients undergoing epilepsy is still insufficiently treated. Therefore, the search for more effective AEDs that treat or prevent epilepsy with minimal side effects is necessary. In this study, a series of 2-(1-(4-Methoxyphenyl)-2- phenylethylidene) hydrazine carboximidamide derivatives were evaluated for their anticonvulsant activities. In the preliminary screening, compounds FA-72, FA-92, and FA-102 (100 ug/rat) showed promising anticonvulsant activities against tonic-clonic seizure when administered by intracerebroventricular (i.c.v.) microinjection 15 min before subcutaneous pentylenetetrazole (scPTZ) administration, while FA-62 and FA-82 did not represent protection against seizures in scPTZ model. The most active compound FA-102 which had a high-degree protection against the PTZ-induced seizures was selected for further pharmacological evaluation using patch-clamp technique. Rat brain slice consisted of dentate gyrus (DG) of hippocampal area were prepared. In voltage clamp recording, the effect of FA-102 on excitatory and inhibitory post synaptic currents (EPSCs and IPSCs, respectively) in the DG granule cells was evaluated. Also, in current clamp recording, both the number and the shape of action potentials (APs) in depolarizing currents were evaluated. The results showed no change in the number nor in the shape of APs after bath application of FA-102. Voltage clamp recording showed significant increase in the number, but not the amplitude of IPSCs after FA-102 bath application. Also, the number of EPSCs tends to decrease, although not significant, compared with control conditions. Our results showed anticonvulsant effects of tested compound with a possible action on inhibitory GABA transmitter release.