Comparing the dopaminergic neurotoxic effects of benzylpiperazine and benzoylpiperazine.

Abstract

Benzylpiperazine has been designated as Schedule I substance under the Controlled Substances Act by Drug Enforcement Administration. Benzylpiperazine is a piperazine derivative, elevates both dopamine and serotonin extracellular levels producing stimulatory and hallucinogenic effects, respectively, similar to methylenedioxymethamphetamine (MDMA). However, the comparative neurotoxic effects of Piperazine derivatives (benzylpiperazine and benzoylpiperazine) have not been elucidated. Here, piperazine derivatives (benzylpiperazine and benzoylpiperazine) were synthesized in our lab and the mechanisms of cellular-based neurotoxicity were elucidated in a dopaminergic human neuroblastoma cell line (SH-SY5Y). We evaluated the in vitro effects of benzylpiperazine and benzoylpiperazine on the generation of reactive oxygen species, lipid peroxidation, mitochondrial complex-I activity, catalase activity, superoxide dismutase activity, glutathione content, Bax, caspase-3, Bcl-2 and tyrosine hydroxylase expression. Benzylpiperazine and benzoylpiperazine induced oxidative stress, inhibited mitochondrial functions and stimulated apoptosis. This study provides a germinal assessment of the neurotoxic mechanisms induced by piperazine derivatives that lead to neuronal cell death.

• Authors: Daniel P Katz, Mohammed Majrashi, Sindhu Ramesh, Manoj Govindarajulu, Dwipayan Bhattacharya, Subhrajit Bhattacharya, Aimen Shlghom, Chastity Bradford, Vishnu Suppiramaniam, Jack Deruiter, C Randall Clark, Muralikrishnan Dhanasekaran
• Journal: Toxicology mechanisms and methods (Toxicol Mech Methods) Vol. 28 Issue 3 Pg. 177-186 (Mar 2018) ISSN: 1537-6524 [Electronic] England
• PMID: 28874085 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Apoptosis Regulatory Proteins
• Biomarkers
• Designer Drugs
• Dopamine Agonists
• Hallucinogens
• Nerve Tissue Proteins
• Piperazines
• Reactive Oxygen Species
• 1-benzylpiperazine
• N,N'-dibenzoylpiperazine
• Electron Transport Complex I

Topics

• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (agonists, antagonists & inhibitors, metabolism)
• Biomarkers (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Designer Drugs (chemistry, toxicity)
• Dopamine Agonists (chemistry, toxicity)
• Dopaminergic Neurons (cytology, drug effects, metabolism)
• Electron Transport Complex I (antagonists & inhibitors, metabolism)
• Hallucinogens (chemistry, toxicity)
• Humans
• Lipid Peroxidation (drug effects)
• Mitochondria (drug effects, enzymology, metabolism)
• Molecular Structure
• Nerve Tissue Proteins (agonists, antagonists & inhibitors, metabolism)
• Osmolar Concentration
• Oxidative Stress (drug effects)
• Piperazines (chemistry, toxicity)
• Reactive Oxygen Species (agonists, metabolism)