Affiliation:
1. Sechenov University, Moscow, Russian Federation
2. N.P. Ogarev Mordovia State University, Saransk, Russian Federation
Abstract
The anticonvulsant activity of 2-aminoethanesulfonic derivatives - magnesium bis-acetamino-2-aminoethanesulfonate (LHT-317) and zinc cyclo-bis-acetamino-2-aminoethanesulphonate (LHT-318) derivatives was studied in the model of pilacorpine epileptogenesis. The studies were performed on 30 white laboratory rats, in which epilepsy was modeled by intraperitoneal administration of pilocarpine hydrochloride at a dose of 320 mg/kg. Within 4 weeks after the formation of epilepsy rats were got intragastrically LHT-31, LHT-318 and Carbamazepine at doses of 2.5% and 5% of the LD50 determined for rats with this route of administration. Carbamazepine was used as the reference drug. The frequency, duration and severity of seizures were assessed using the Krushinsky scale. Morphological studies of the brain in the hippocampus and dentate sulcus were profiled by Nissl staining using 0.4% cresyl violet. The results were evaluated using an Olympus Bx50 digital microscope, x400 magnification over an area of 1000 µm2. The zinc salt of 2-aminoethanesulfonic acid LHT-318 exhibited anticonvulsant properties: it reduced the severity of acute convulsive paroxysm, prevented the formation of spontaneous convulsive activity, and was comparable in activity to the reference drug carbamazepine. LHT-317 did not demonstrate antiepileptic activity in this model. Compounds LHT-317 and LHT-318 at course administration prevented the depth of morphological changes characteristic of pilocarpine epileptogenesis, while it should be emphasized that complete prevention of morphological disorders is not observed in any case. Thus, based on the study, we can conclude that the zinc cyclic salt of 2-aminoethanesulfonic acid can be considered as a potential drug for the treatment of epilepsy.