Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives

Simmler, Linda D. and Rickli, Anna and Schramm, York and Hoener, Marius C. and Liechti, Matthias E.. (2014) Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives. Biochemical Pharmacology, 88 (2). pp. 237-244.

[img] PDF - Accepted Version

Official URL: http://edoc.unibas.ch/56166/

Downloads: Statistics Overview


Aminoindanes, piperazines, and pipradrol derivatives are novel psychoactive substances found in "Ecstasy" tablets as replacements for 3,4-methylenedioxymethamphetamine (MDMA) or substances sold as "ivory wave." The pharmacology of these MDMA- and methylphenidate-like substances is poorly known. We characterized the pharmacology of the aminoindanes 5,6-methylenedioxy-2-aminoindane (MDAI), 5-iodoaminoindane (5-IAI), and 2-aminoindane (2-AI), the piperazines meta-chlorophenylpiperazine (m-CPP), trifluoromethylphenylpiperazine (TFMPP), and 1-benzylpiperazine (BZP), and the pipradrol derivatives desoxypipradrol (2-diphenylmethylpiperidine [2-DPMP]), diphenylprolinol (diphenyl-2-pyrrolidinemethanol [D2PM]), and methylphenidate. We investigated norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine [5-HT]) uptake inhibition using human embryonic kidney 293 (HEK 293) cells that express the respective human monoamine transporters (NET, DAT, and SERT). We also evaluated the drug-induced efflux of NE, DA, and 5-HT from monoamine-preloaded cells and the binding affinity to monoamine transporters and receptors, including trace amine-associated receptor 1 (TAAR1). 5-IAI and MDAI preferentially inhibited the SERT and NET and released 5-HT. 2-AI interacted with the NET. BZP blocked the NET and released DA. m-CPP and TFMPP interacted with the SERT and serotonergic receptors. The pipradrol derivatives were potent and selective catecholamine transporter blockers without substrate releasing properties. BZP, D2PM, and 2-DPMP lacked serotonergic activity and TAAR1 binding, in contrast to the aminoindanes and phenylpiperazines. In summary, all of the substances were monoamine transporter inhibitors, but marked differences were found in their DAT vs. SERT inhibition profiles, release properties, and receptor interactions. The pharmacological profiles of D2PM and 2-DPMP likely predict a high abuse liability.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Psychopharmacology Research (Liechti)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Neuropharmacology (Simmler)
UniBasel Contributors:Liechti, Matthias Emanuel and Simmler, Linda
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
edoc DOI:
Last Modified:27 Apr 2023 03:10
Deposited On:04 Dec 2017 10:25

Repository Staff Only: item control page