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.

CONCLUSION:

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: Shikha Kumari, Chandra Bhushan Mishra, Manisha Tiwari
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 68 Issue 2 Pg. 250-8 (Apr 2016) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 26922524 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Chemical References

• Anticonvulsants
• Antidepressive Agents
• Phenylurea Compounds
• Piperazines
• Semicarbazides
• Piperazine
• thiosemicarbazide
• N-phenylurea
• 3-Mercaptopropionic Acid
• Pentylenetetrazole

Topics

• 3-Mercaptopropionic Acid (pharmacology)
• Animals
• Anticonvulsants (pharmacology)
• Antidepressive Agents (pharmacology)
• Disease Models, Animal
• Electroshock (methods)
• Mice
• Pentylenetetrazole (pharmacology)
• Phenylurea Compounds (pharmacology)
• Piperazine
• Piperazines (pharmacology)
• Rats
• Rats, Wistar
• Seizures (chemically induced, drug therapy)
• Semicarbazides (pharmacology)
• Status Epilepticus (drug therapy)