title: Estrogenic effects and their action mechanism of the major active components of party pill drugs.
abstract: Benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) are commonly used constituents of party pill drugs. They are reported to induce psychoactive effects such as euphoria and provide effects similar with other illicit drugs such as methylenedioxymethamphetamine (MDMA). A great deal of evidence has proven that party pills, as alternatives for MDMA, exert harmful effects on users. However, their toxicological effects have not been fully understood and endocrine disruptive effects are still unknown. In this study, we identified estrogenic effects of BZP and TFMPP by using in vitro and in vivo assays. BZP and TFMPP stimulated cell proliferation in a dose-dependent manner, while co-treatment with tamoxifen and BZP or TFMPP showed a decrease of E(2)-induced cell proliferation. In an estrogen sensitive reporter gene assay, BZP and TFMPP significantly increased transcriptional activities of party pill drugs. In addition, ER-related genes, PR and pS2, were significantly stimulated by BZP and TFMPP. These results indicated that BZP and TFMPP could have estrogenic activities related to the ER-mediated pathway. Unlike the in vitro assay results, BZP and TFMPP did not show significant effects on weight increase in a rodent uterotrophic assay. However, further studies would be necessary to verify the estrogenic activities of BZP and TFMPP by a chronic exposure animal study.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon dong, Jangan-gu, Suwon, Kyeonggi-do 440-746, South Korea.
authors.forename: Cho Rong
authors.initials: CR
authors.lastname: Min
authors.forename: Mi Jie
authors.initials: MJ
authors.lastname: Kim
authors.forename: Yong Joo
authors.initials: YJ
authors.lastname: Park
authors.forename: Ha Ryong
authors.initials: HR
authors.lastname: Kim
authors.forename: Soo Yeun
authors.initials: SY
authors.lastname: Lee
authors.forename: Kyu Hyuck
authors.initials: KH
authors.lastname: Chung
authors.forename: Seung Min
authors.initials: SM
authors.lastname: Oh
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects / Q000235:genetics; D006801:Humans; D013287:Illicit Drugs / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010879:Piperazines / Q000633:toxicity*; D017366:Serotonin Receptor Agonists / Q000633:toxicity*; D013629:Tamoxifen / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000254:growth & development
chemical_list: D000697:Central Nervous System Stimulants; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D013287:Illicit Drugs; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D013629:Tamoxifen; C018406:1-(3-trifluoromethylphenyl)piperazine; C006737:1-benzylpiperazine