title: Pharmacological evaluation of novel 1-[4-(4-benzo[1,3]dioxol-5-ylmethyl-piperazin-1-yl)-phenyl]-3-phenyl-urea as potent anticonvulsant and antidepressant agent.
abstract: BACKGROUND
  Earlier, we have identified a number of piperazine derivatives having good anticonvulsant activity in vivo and as a part of our ongoing search for potent anticonvulsant agent, we herein describes the synthesis of an aryl piperazine derivative "1-[4-(4-benzo[1,3]dioxol-5-ylmethyl-piperazin-1-yl)-phenyl]-3-phenyl-urea" (BPPU). The anticonvulsant and antidepressant activity of BPPU was checked in various in vivo models.
  
  
  METHODS
  Anticonvulsant activity was assessed in maximal electroshock test (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure tests. Moreover, plausible mechanistic studies were also performed by using several chemical induced seizure models. The antidepressant activity of BPPU was checked in forced swim test (FST) and tail suspension test (TST) in mice. Drug safety profile was studied in sub-acute toxicity rat model at a dose of 100mg/kg, per oral for 14 days.
  
  
  RESULTS
  BPPU exhibited excellent protection against seizures induced by MES and scPTZ in mice as well as rats. In pilocarpine induced model of status epilepticus (SE), BPPU demonstrated 50% protection at a dose of 100mg/kg in rats. BPPU also successfully inhibited seizures induced by 3-mercaptopropionic acid (3-MPA) and thiosemicarbazide (TSC) in mice thus, suggested that BPPU might influence GABA-ergic neurotransmission in the brain. Moreover, BPPU showed good antidepressant activity and did not exhibit any significant toxicity.
  
  
  CONCLUSIONS
  BPPU displayed broad spectrum of anticonvulsant activity in several seizure models along with satisfactory antidepressant activity. Therefore, BPPU may be further developed as a potential therapeutic agent for therapy of epileptic disorders.
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, New Delhi, India.
authors.forename: Shikha
authors.initials: S
authors.lastname: Kumari
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, New Delhi, India.
authors.forename: Chandra Bhushan
authors.initials: CB
authors.lastname: Mishra
authors.affiliation: Bio-Organic Chemistry Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, New Delhi, India. Electronic address: mtiwari07@gmail.com.
authors.forename: Manisha
authors.initials: M
authors.lastname: Tiwari
mesh_terms: D015097:3-Mercaptopropionic Acid / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004597:Electroshock / Q000379:methods; D051379:Mice; D010433:Pentylenetetrazole / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D000077489:Piperazine; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D012663:Semicarbazides / Q000494:pharmacology; D013226:Status Epilepticus / Q000188:drug therapy
chemical_list: D000927:Anticonvulsants; D000928:Antidepressive Agents; D010671:Phenylurea Compounds; D010879:Piperazines; D012663:Semicarbazides; D000077489:Piperazine; C005151:thiosemicarbazide; C580738:N-phenylurea; D015097:3-Mercaptopropionic Acid; D010433:Pentylenetetrazole
keywords: Anticonvulsant; Antidepressant; Piperazine; Synthesis; Toxicity