Keywords
Abstract
The high prevalence of acquired and congenital epilepsies, the inadequate efficacy of standard therapies in one-third of refractory cases, and the numerous side effects of anticonvulsant drugs have prompted the search for new drugs and methods for the treatment of epilepsies. According to preliminary studies, representatives of a new class of thiopyrano[2,3-d]thiazole compounds are promising, including the leader in the anticonvulsant screening rel-N-(4-chlorophenyl)-3-[(5aR,11bR)-2-oxo-5a,11b-dihydro-2H,5H- chromeno[4’,3’:4,5]thiopyrano[2,3-d][1,3]thiazol-3(6H)-yl]propanamide (laboratory code Les-3384).
The aim of the study was to determine the effect of rel-N-(4-chlorophenyl)-3-[(5aR,11bR)-2-oxo-5a,11b- dihydro-2H,5H-chromeno[4’,3’:4,5]thiopyrano[2,3-d][1,3]thiazol-3(6H)-yl]propanamide on behavioral responses in the open field test, muscle tone and movement coordination, and pain sensitivity.
The experiments were performed in white male non-linear mice in the laboratory of the Educational and Research Institute of Applied Pharmacy of the National University of Pharmacy (Kharkiv). The test compound Les-3384 (100 mg/kg) and the comparator carbamazepine (40 mg/kg) were administered once intragastrically in the form of a tween-80 stabilized suspension 30 min before the test. Control animals received an equal volume of purified water intragastrically. Effects on motor, exploratory and emotional responses were assessed by the open field test, muscle tone and movement coordination by the rotarod test, and pain sensitivity by the «Hot plate test».
It was found that Les-3384 tends to reduce motor activity in mice and thus the sum of all activities in the open field test. Compared to the effect of carbamazepine, which increases the number of emotional responses, the compound significantly reduce them. According to the results of the rotarod test, there were no disturbances in muscle tone and coordination of the animals’ movements. This suggests that Les-3384 does not have side effects associated with CNS depression, which are inherent to most antiepileptic drugs. No analgesic properties of Les-3384 were found in the study.
The promising anticonvulsant rel-N-(4-chlorophenyl)-3-[(5aR,11bR)-2-oxo-5a,11b-dihydro-2H,5H- chromeno[4’,3’:4,5]thiopyrano[ 2,3-d][1,3]thiazol-3(6H)-yl]propanamide was found to have no adverse effects on behavioral reactivity, muscle tone and movement sequence. This compound also has no analgesic properties, which distinguishes it from a number of known anticonvulsants.