Characterization and preliminary anticonvulsant assessment of some 1,3,4-thiadiazole derivatives. 2015

Jarogniew J Luszczki, and Monika Karpińska, and Joanna Matysiak, and Andrzej Niewiadomy
Department of Pathophysiology, Medical University of Lublin, Lublin, Poland; Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland. Electronic address: jarogniew.luszczki@gmail.com.

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.

UI MeSH Term Description Entries
D008297 Male Males
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D004597 Electroshock Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. Electroconvulsive Shock,Electroconvulsive Shocks,Electroshocks,Shock, Electroconvulsive,Shocks, Electroconvulsive
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic
D012640 Seizures Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder." Absence Seizure,Absence Seizures,Atonic Absence Seizure,Atonic Seizure,Clonic Seizure,Complex Partial Seizure,Convulsion,Convulsions,Convulsive Seizure,Convulsive Seizures,Epileptic Seizure,Epileptic Seizures,Generalized Absence Seizure,Generalized Tonic-Clonic Seizures,Jacksonian Seizure,Myoclonic Seizure,Non-Epileptic Seizure,Nonepileptic Seizure,Partial Seizure,Seizure,Seizures, Convulsive,Seizures, Focal,Seizures, Generalized,Seizures, Motor,Seizures, Sensory,Tonic Clonic Seizure,Tonic Seizure,Tonic-Clonic Seizure,Atonic Absence Seizures,Atonic Seizures,Clonic Seizures,Complex Partial Seizures,Convulsion, Non-Epileptic,Generalized Absence Seizures,Myoclonic Seizures,Non-Epileptic Seizures,Nonepileptic Seizures,Partial Seizures,Petit Mal Convulsion,Seizures, Auditory,Seizures, Clonic,Seizures, Epileptic,Seizures, Gustatory,Seizures, Olfactory,Seizures, Somatosensory,Seizures, Tonic,Seizures, Tonic-Clonic,Seizures, Vertiginous,Seizures, Vestibular,Seizures, Visual,Single Seizure,Tonic Seizures,Tonic-Clonic Seizures,Absence Seizure, Atonic,Absence Seizure, Generalized,Absence Seizures, Atonic,Absence Seizures, Generalized,Auditory Seizure,Auditory Seizures,Clonic Seizure, Tonic,Clonic Seizures, Tonic,Convulsion, Non Epileptic,Convulsion, Petit Mal,Convulsions, Non-Epileptic,Focal Seizure,Focal Seizures,Generalized Seizure,Generalized Seizures,Generalized Tonic Clonic Seizures,Generalized Tonic-Clonic Seizure,Gustatory Seizure,Gustatory Seizures,Motor Seizure,Motor Seizures,Non Epileptic Seizure,Non Epileptic Seizures,Non-Epileptic Convulsion,Non-Epileptic Convulsions,Olfactory Seizure,Olfactory Seizures,Partial Seizure, Complex,Partial Seizures, Complex,Seizure, Absence,Seizure, Atonic,Seizure, Atonic Absence,Seizure, Auditory,Seizure, Clonic,Seizure, Complex Partial,Seizure, Convulsive,Seizure, Epileptic,Seizure, Focal,Seizure, Generalized,Seizure, Generalized Absence,Seizure, Generalized Tonic-Clonic,Seizure, Gustatory,Seizure, Jacksonian,Seizure, Motor,Seizure, Myoclonic,Seizure, Non-Epileptic,Seizure, Nonepileptic,Seizure, Olfactory,Seizure, Partial,Seizure, Sensory,Seizure, Single,Seizure, Somatosensory,Seizure, Tonic,Seizure, Tonic Clonic,Seizure, Tonic-Clonic,Seizure, Vertiginous,Seizure, Vestibular,Seizure, Visual,Seizures, Generalized Tonic-Clonic,Seizures, Nonepileptic,Sensory Seizure,Sensory Seizures,Single Seizures,Somatosensory Seizure,Somatosensory Seizures,Tonic Clonic Seizures,Tonic-Clonic Seizure, Generalized,Tonic-Clonic Seizures, Generalized,Vertiginous Seizure,Vertiginous Seizures,Vestibular Seizure,Vestibular Seizures,Visual Seizure,Visual Seizures
D013830 Thiadiazoles Heterocyclic compounds composed of a five-membered heterocyclic ring which contains one sulfur and two nitrogen atoms. Thiadiazole
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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