PMID- 28874085
OWN - NLM
STAT- MEDLINE
DCOM- 20180820
LR  - 20191210
IS  - 1537-6524 (Electronic)
IS  - 1537-6516 (Linking)
VI  - 28
IP  - 3
DP  - 2018 Mar
TI  - Comparing the dopaminergic neurotoxic effects of benzylpiperazine and 
      benzoylpiperazine.
PG  - 177-186
LID - 10.1080/15376516.2017.1376024 [doi]
AB  - 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.
FAU - Katz, Daniel P
AU  - Katz DP
AD  - a Department of Drug Discovery and Development , Harrison School of Pharmacy, 
      Auburn University , Auburn , AL , USA.
FAU - Majrashi, Mohammed
AU  - Majrashi M
AD  - a Department of Drug Discovery and Development , Harrison School of Pharmacy, 
      Auburn University , Auburn , AL , USA.
AD  - b Department of Pharmacology, Faculty of Medicine , Jeddah University , Jeddah , 
      KSA.
FAU - Ramesh, Sindhu
AU  - Ramesh S
AD  - a Department of Drug Discovery and Development , Harrison School of Pharmacy, 
      Auburn University , Auburn , AL , USA.
FAU - Govindarajulu, Manoj
AU  - Govindarajulu M
AD  - a Department of Drug Discovery and Development , Harrison School of Pharmacy, 
      Auburn University , Auburn , AL , USA.
FAU - Bhattacharya, Dwipayan
AU  - Bhattacharya D
AD  - a Department of Drug Discovery and Development , Harrison School of Pharmacy, 
      Auburn University , Auburn , AL , USA.
FAU - Bhattacharya, Subhrajit
AU  - Bhattacharya S
AD  - a Department of Drug Discovery and Development , Harrison School of Pharmacy, 
      Auburn University , Auburn , AL , USA.
FAU - Shlghom, Aimen
AU  - Shlghom A
AD  - c Department of Biology, College of Arts and Sciences , Tuskegee University , 
      Tuskegee , AL , USA.
FAU - Bradford, Chastity
AU  - Bradford C
AD  - c Department of Biology, College of Arts and Sciences , Tuskegee University , 
      Tuskegee , AL , USA.
FAU - Suppiramaniam, Vishnu
AU  - Suppiramaniam V
AD  - a Department of Drug Discovery and Development , Harrison School of Pharmacy, 
      Auburn University , Auburn , AL , USA.
FAU - Deruiter, Jack
AU  - Deruiter J
AD  - a Department of Drug Discovery and Development , Harrison School of Pharmacy, 
      Auburn University , Auburn , AL , USA.
FAU - Clark, C Randall
AU  - Clark CR
AD  - a Department of Drug Discovery and Development , Harrison School of Pharmacy, 
      Auburn University , Auburn , AL , USA.
FAU - Dhanasekaran, Muralikrishnan
AU  - Dhanasekaran M
AD  - a Department of Drug Discovery and Development , Harrison School of Pharmacy, 
      Auburn University , Auburn , AL , USA.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20170928
PL  - England
TA  - Toxicol Mech Methods
JT  - Toxicology mechanisms and methods
JID - 101134521
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Biomarkers)
RN  - 0 (Designer Drugs)
RN  - 0 (Dopamine Agonists)
RN  - 0 (Hallucinogens)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Piperazines)
RN  - 0 (Reactive Oxygen Species)
RN  - 3UG152ZU0E (1-benzylpiperazine)
RN  - 964Y2A1KU8 (N,N'-dibenzoylpiperazine)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/agonists/antagonists & inhibitors/metabolism
MH  - Biomarkers/metabolism
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Designer Drugs/chemistry/toxicity
MH  - Dopamine Agonists/chemistry/*toxicity
MH  - Dopaminergic Neurons/cytology/*drug effects/metabolism
MH  - Electron Transport Complex I/antagonists & inhibitors/metabolism
MH  - Hallucinogens/chemistry/*toxicity
MH  - Humans
MH  - Lipid Peroxidation/drug effects
MH  - Mitochondria/drug effects/enzymology/metabolism
MH  - Molecular Structure
MH  - Nerve Tissue Proteins/agonists/antagonists & inhibitors/metabolism
MH  - Osmolar Concentration
MH  - Oxidative Stress/*drug effects
MH  - Piperazines/chemistry/*toxicity
MH  - Reactive Oxygen Species/agonists/metabolism
OTO - NOTNLM
OT  - Piperazine designer drugs
OT  - apoptosis
OT  - mitochondrial functions
OT  - monoamine neurotransmission
OT  - neurotoxicity
EDAT- 2017/09/07 06:00
MHDA- 2018/08/21 06:00
CRDT- 2017/09/07 06:00
PHST- 2017/09/07 06:00 [pubmed]
PHST- 2018/08/21 06:00 [medline]
PHST- 2017/09/07 06:00 [entrez]
AID - 10.1080/15376516.2017.1376024 [doi]
PST - ppublish
SO  - Toxicol Mech Methods. 2018 Mar;28(3):177-186. doi: 10.1080/15376516.2017.1376024. 
      Epub 2017 Sep 28.