Design and evaluation of pharmacological properties of a new 1,3,4-thiadiazolylamide derivative of 2-propylpentanoic acid

Introduction: The use of the pharmacophoric approach is a promising direction for modifying chemical structure 2-propylpentanoic (valproic) acid in order to obtain new drugs.
 Materials and methods: In experiments on mice, acute toxicity, neurotoxicity, antiepileptic activity analgesic effect N-(5-ethyl-1,3,4-thiadiazol-2-yl)-2-propylpentanamide (valprazolamide) were evaluated. LD50 was determined by probit analysis. Neurotoxicity rotarod test bar mice. effects valprazolamide exploratory behavior mice open field light/dark transition Its tested against seizures induced maximal electroshock, pentylenetetrazole(scPTZ); isoniazid, thiosemicarbazide, pilocarpine, camphor. studied hot plate test.
 Results discussion: obtained introducing pharmacophores into acid: substituted amide group an electron-donor domain 1,3,4-thiadiazole. value intraperitoneal administration derivative 924.8 mg/kg, TD50 456.7 mg/kg 546.7 respectively. suppression orienting responses animals noted when it administered neurotoxic doses. Valprazolamide showed most models MES, scPTZ isoniazid antagonism tests. ED50 values 138.4 74.5 126.8 therapeutic indices these epilepsy 6.7; 12.4; 7.3, protective index – 3.3; 6.1 3.6, test, increased latency period before defensive response thermal stimulus (ED50 165 mg/kg).
 Conclusion: 1,3,4-thiadiazolylamide with activities, which belongs low-toxic agents.