title: Neurochemical profiles of some novel psychoactive substances.
abstract: Fourteen substances from the class of drugs sometimes known as "legal highs" were screened against a battery of human receptors in binding assays, and their potencies as inhibitors of monoamine uptake determined in functional in vitro assays. Thirteen of the test substances acted as inhibitors of monoamine uptake at submicromolar concentrations, including 9 potent inhibitors of the dopamine transporter (DAT), 12 potent inhibitors of the norepinephrine transporter (NET) and 4 potent inhibitors of the serotonin transporter (SERT). Seven compounds acted as submicromolar inhibitors of both DAT and NET, and three substances 1-(benzofuran-5-yl)propan-2-amine (5-APB), 1-naphthalen-2-yl-2-pyrrolidin-1-ylpentan-1-one hydrochloride ("naphyrone") and 1-naphthalen-1-yl-2-pyrrolidin-1-ylpentan-1-one hydrochloride ("1-naphyrone") were submicromolar inhibitors of all three monoamine transporters. There was a lack of correlation between results of functional uptake experiments and in vitro binding assays for the monoamine transporters. There was also no correlation between the human behavioral effects of the substances and the results of bindings assays for a range of receptor targets, although 1-(benzofuran-5-yl)propan-2-amine (5-APB), 1-(benzofuran-6-yl)propan-2-amine hydrochloride (6-APB) and 5-iodo-2,3-dihydro-1H-inden-2-amine hydrochloride (5-iodo-aminoindane) exhibited <100 nM affinities for 5HT(2B) and α(2C) receptors. Functional assays revealed that 5-APB and 6-APB were potent full agonists at 5HT(2B) receptors.
authors.affiliation: Department of Pharmacology, University of Oxford, UK. les.iversen@pharm.ox.ac.uk
authors.forename: Les
authors.initials: L
authors.lastname: Iversen
authors.forename: Simon
authors.initials: S
authors.lastname: Gibbons
authors.forename: Ric
authors.initials: R
authors.lastname: Treble
authors.forename: Vincent
authors.initials: V
authors.lastname: Setola
authors.forename: Xi-Ping
authors.initials: XP
authors.lastname: Huang
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
mesh_terms: D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D009448:Neurochemistry; D011619:Psychotropic Drugs / Q000494:pharmacology*
chemical_list: D026901:Membrane Transport Proteins; D011619:Psychotropic Drugs