PMID- 15542717
OWN - NLM
STAT- MEDLINE
DCOM- 20050218
LR  - 20181201
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1025
DP  - 2004 Oct
TI  - Effects of "Legal X" piperazine analogs on dopamine and serotonin release in rat 
      brain.
PG  - 189-97
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) is a popular illicit drug that evokes 
      transporter-mediated release of serotonin (5-HT) and dopamine (DA) from nerve 
      cells. Recently, drug users have ingested combinations of the piperazine analogs, 
      1-benzylpiperazine (BZP) and 1-(m-trifluoromethylphenyl)piperazine (TFMPP), in an 
      attempt to mimic the subjective effects of MDMA. In the present study, we 
      compared neurochemical effects of MDMA, BZP, and TFMPP in rat brain. The ability 
      of MDMA, BZP, and TFMPP to stimulate efflux of [3H]5-HT and [3H]MPP+ (a DA 
      transporter substrate) was determined in vitro using release assays in 
      synaptosomes. The ability of these drugs to increase extracellular 5-HT and DA in 
      vivo was assessed using intracranial microdialysis in nucleus accumbens. MDMA 
      stimulated transporter-mediated release of 5-HT (EC50 = 58 nM) and MPP+ (EC50 = 
      119 nM). BZP was a selective releaser of MPP+ (EC50 = 175 nM), whereas TFMPP was 
      a selective releaser of 5-HT (EC50 = 121 nM). MDMA injections (1 and 3 mg/kg, 
      i.v.) increased dialysate 5-HT and DA in a dose-related manner, but actions on 
      5-HT were predominant. BZP (3 and 10 mg/kg, i.v.) elevated dialysate DA and 5-HT, 
      while TFMPP (3 and 10 mg/kg, i.v.) elevated only 5-HT. The coadministration of 
      BZP plus TFMPP (BZP/TFMPP) produced marked elevations in extracellular 5-HT and 
      DA that mirrored the effects of MDMA. At the high dose of BZP/TFMPP (10 mg/kg, 
      i.v.), the rise in dialysate DA exceeded the summed effects of the drugs alone. 
      Our results support the hypothesis that the BZP/TFMPP combination mimics the 
      neurochemical mechanism of MDMA, providing a basis for recreational use of these 
      agents. Additionally, the findings suggest possible drug-drug synergism when 
      piperazine drugs are coadministered at high doses.
FAU - Baumann, Michael H
AU  - Baumann MH
AD  - Clinical Psychopharmacology Section, IRP, NIDA, National Institutes of Health, 
      Baltimore, Maryland 21224, USA. mbaumann@intra.nida.nih.gov
FAU - Clark, Robert D
AU  - Clark RD
FAU - Budzynski, Allison G
AU  - Budzynski AG
FAU - Partilla, John S
AU  - Partilla JS
FAU - Blough, Bruce E
AU  - Blough BE
FAU - Rothman, Richard B
AU  - Rothman RB
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Piperazines)
RN  - 1RTM4PAL0V (Piperazine)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/metabolism
MH  - Dopamine/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/analogs & derivatives/*pharmacology
MH  - Piperazine
MH  - Piperazines/chemistry/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
EDAT- 2004/11/16 09:00
MHDA- 2005/02/19 09:00
CRDT- 2004/11/16 09:00
PHST- 2004/11/16 09:00 [pubmed]
PHST- 2005/02/19 09:00 [medline]
PHST- 2004/11/16 09:00 [entrez]
AID - 1025/1/189 [pii]
AID - 10.1196/annals.1316.024 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2004 Oct;1025:189-97. doi: 10.1196/annals.1316.024.