Jarogniew J Luszczki1, Monika Karpińska2, Joanna Matysiak3, Andrzej Niewiadomy4. 1. Department of Pathophysiology, Medical University of Lublin, Lublin, Poland; Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland. Electronic address: jarogniew.luszczki@gmail.com. 2. Institute of Industrial Organic Chemistry, Warszawa, Poland. 3. Department of Chemistry, University of Life Sciences in Lublin, Lublin, Poland. 4. Institute of Industrial Organic Chemistry, Warszawa, Poland; Department of Chemistry, University of Life Sciences in Lublin, Lublin, Poland.
Abstract
BACKGROUND: The aim of this study was to perform the anticonvulsant screening test to select some 1,3,4-thiadiazole derivatives that could offer a distinct protection against maximal electroshock (MES)-induced seizures in mice. METHODS: The screening test was performed for 13 tested compounds administered intraperitoneally (ip) in a constant dose of 300 mg/kg at various pretreatment times (i.e., 15, 30, 60 and 120 min) before the MES test. Additionally, the active compounds in the screening test were subsequently subjected to the MES test that allowed determination of their median effective doses (ED50 values). RESULTS: Only 2 out of 13 tested 1,3,4-thiadiazole derivatives i.e., 5-butyl-; and 5-heptyl-substituted in the heterocyclic ring 1,3,4-thiadiazoles produced a distinct protection against MES-induced tonic seizures in mice. Time-course and dose-response effects revealed that 5-butyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole produced its maximum anticonvulsant action at 15 min after its ip administration to mice. In contrast, 5-heptyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole exerted the maximum anticonvulsant action at 60 min after its ip administration to mice. The ED50 values for 5-butyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole ranged between 247 and >500 mg/kg, whereas those for 5-heptyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole ranged between 233 and >500 mg/kg. CONCLUSIONS: 5-Butyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole and 5-heptyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole could become potentially favorable antiepileptic drugs, if the results from this study were to be extrapolated into clinical settings.
BACKGROUND: The aim of this study was to perform the anticonvulsant screening test to select some 1,3,4-thiadiazole derivatives that could offer a distinct protection against maximal electroshock (MES)-induced seizures in mice. METHODS: The screening test was performed for 13 tested compounds administered intraperitoneally (ip) in a constant dose of 300 mg/kg at various pretreatment times (i.e., 15, 30, 60 and 120 min) before the MES test. Additionally, the active compounds in the screening test were subsequently subjected to the MES test that allowed determination of their median effective doses (ED50 values). RESULTS: Only 2 out of 13 tested 1,3,4-thiadiazole derivatives i.e., 5-butyl-; and 5-heptyl-substituted in the heterocyclic ring 1,3,4-thiadiazoles produced a distinct protection against MES-induced tonic seizures in mice. Time-course and dose-response effects revealed that 5-butyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole produced its maximum anticonvulsant action at 15 min after its ip administration to mice. In contrast, 5-heptyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole exerted the maximum anticonvulsant action at 60 min after its ip administration to mice. The ED50 values for 5-butyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole ranged between 247 and >500 mg/kg, whereas those for 5-heptyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole ranged between 233 and >500 mg/kg. CONCLUSIONS:5-Butyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole and 5-heptyl-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole could become potentially favorable antiepileptic drugs, if the results from this study were to be extrapolated into clinical settings.