Tags

Type your tag names separated by a space and hit enter

Effects of "Legal X" piperazine analogs on dopamine and serotonin release in rat brain.
Ann N Y Acad Sci 2004; 1025:189-97AN

Abstract

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.

Authors+Show Affiliations

Clinical Psychopharmacology Section, IRP, NIDA, National Institutes of Health, Baltimore, Maryland 21224, USA. mbaumann@intra.nida.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15542717

Citation

Baumann, Michael H., et al. "Effects of "Legal X" Piperazine Analogs On Dopamine and Serotonin Release in Rat Brain." Annals of the New York Academy of Sciences, vol. 1025, 2004, pp. 189-97.
Baumann MH, Clark RD, Budzynski AG, et al. Effects of "Legal X" piperazine analogs on dopamine and serotonin release in rat brain. Ann N Y Acad Sci. 2004;1025:189-97.
Baumann, M. H., Clark, R. D., Budzynski, A. G., Partilla, J. S., Blough, B. E., & Rothman, R. B. (2004). Effects of "Legal X" piperazine analogs on dopamine and serotonin release in rat brain. Annals of the New York Academy of Sciences, 1025, pp. 189-97.
Baumann MH, et al. Effects of "Legal X" Piperazine Analogs On Dopamine and Serotonin Release in Rat Brain. Ann N Y Acad Sci. 2004;1025:189-97. PubMed PMID: 15542717.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of "Legal X" piperazine analogs on dopamine and serotonin release in rat brain. AU - Baumann,Michael H, AU - Clark,Robert D, AU - Budzynski,Allison G, AU - Partilla,John S, AU - Blough,Bruce E, AU - Rothman,Richard B, PY - 2004/11/16/pubmed PY - 2005/2/19/medline PY - 2004/11/16/entrez SP - 189 EP - 97 JF - Annals of the New York Academy of Sciences JO - Ann. N. Y. Acad. Sci. VL - 1025 N2 - 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. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/15542717/Effects_of_"Legal_X"_piperazine_analogs_on_dopamine_and_serotonin_release_in_rat_brain_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0077-8923&date=2004&volume=1025&spage=189 DB - PRIME DP - Unbound Medicine ER -