title: Design, Synthesis and Evaluation of the Antidepressant and Anticonvulsant Activities of Triazole-Containing Benzo[d]oxazoles.
abstract: BACKGROUND
  Epilepsy and depression are two of the common diseases seriously threatening life and health of human. A shared neurobiological substrate led to the bidirectional relationship and high comorbid occurrence of the two disorders. Recently, an increasing number of patients with epilepsy (PWE) require some form of antidepressant medication. However, most of the available antidepressants are inadequate for PWE for some reasons. So, the search for novel and increasingly effective drugs with anticonvulsant and antidepressant activities is necessary.
  
  
  METHODS
  A series of 2-substituted-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles (5a-p) were designed and synthesized. Their anticonvulsant activities were evaluated using maximal electroshock shock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. Their antidepressant activities were screened with the forced swimming test (FST).
  
  
  RESULTS
  All the compounds showed anti-MES activities in different degree, among which 5g and 5j were the most promising one with ED50 value of 31.7 and 12.7 mg/kg, respectively. What's more, 5g and 5j also exhibited nice anti-scPTZ activities and low neurotoxicity. Interestingly, these compounds also showed good antidepressant activities in FST. And the efficacy of 5g were also confirmed by a tail suspension test and a open field test. The pretreatment of thiosemicarbazide (an inhibitor of γ- aminobutyric acid synthesis enzyme) significantly increased the ED50 of 5g in MES and reversed the reductions in the immobility time of 5g in FST.
  
  
  CONCLUSIONS
  Triazole-containing benzo[d]oxazole is a good skeleton to develop compounds with both anticonvulsant and antidepressant activities. We have got the compound 5g, which display remarkable antidepressant and anticonvulsant activities, and the GABAergic system was involved in the action mechanism of 5g.
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Song
authors.forename: Bao-Qi
authors.initials: BQ
authors.lastname: Rao
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Cheng
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Zeng
authors.forename: You-Gen
authors.initials: YG
authors.lastname: Luo
authors.affiliation: Medical College, Jinggangshan University, P.O. Box: 343009, Ji'an, Jiangxi, China.
authors.forename: Xian-Qing
authors.initials: XQ
authors.lastname: Deng
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D003198:Computer Simulation; D003866:Depressive Disorder / Q000188:drug therapy; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D018757:GABA Modulators / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D000928:Antidepressive Agents; D001583:Benzoxazoles; D018757:GABA Modulators; D005680:gamma-Aminobutyric Acid
keywords: Antidepressant; anticonvulsant; benzo[d]oxazole; forced swimming test; maximal electroshock; triazole