title: Pharmacological profile of novel psychoactive benzofurans.
abstract: OBJECTIVE
  Benzofurans are newly used psychoactive substances, but their pharmacology is unknown. The aim of the present study was to pharmacologically characterize benzofurans in vitro.
  
  
  METHODS
  We assessed the effects of the benzofurans 5-APB, 5-APDB, 6-APB, 6-APDB, 4-APB, 7-APB, 5-EAPB and 5-MAPDB and benzodifuran 2C-B-FLY on the human noradrenaline (NA), dopamine and 5-HT uptake transporters using HEK 293 cells that express the respective transporters. We also investigated the release of NA, dopamine and 5-HT from monoamine-preloaded cells, monoamine receptor-binding affinity and 5-HT2A and 5-HT2B receptor activation.
  
  
  RESULTS
  All of the benzofurans inhibited NA and 5-HT uptake more than dopamine uptake, similar to methylenedioxymethamphetamine (MDMA) and unlike methamphetamine. All of the benzofurans also released monoamines and interacted with trace amine-associated receptor 1 (TA1 receptor), similar to classic amphetamines. Most benzofurans were partial 5-HT2A receptor agonists similar to MDMA, but also 5-HT2B receptor agonists, unlike MDMA and methamphetamine. The benzodifuran 2C-B-FLY very potently interacted with 5-HT2 receptors and also bound to TA1 receptors.
  
  
  CONCLUSIONS
  Despite very similar structures, differences were found in the pharmacological profiles of different benzofurans and compared with their amphetamine analogues. Benzofurans acted as indirect monoamine agonists that interact with transporters similarly to MDMA. The benzofurans also interacted with 5-HT receptors. This pharmacological profile probably results in MDMA-like entactogenic psychoactive properties. However, benzofurans induce 5-HT2B receptor activation associated with heart valve fibrosis. The pharmacology of 2C-B-FLY indicates predominant hallucinogenic properties and a risk for vasoconstriction.
authors.affiliation: Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Rickli
authors.affiliation: Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
authors.forename: Simone
authors.initials: S
authors.lastname: Kopf
authors.affiliation: Neuroscience Research, pRED, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Marius C
authors.initials: MC
authors.lastname: Hoener
authors.affiliation: Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Liechti
mesh_terms: D001572:Benzofurans / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
chemical_list: D001572:Benzofurans; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011619:Psychotropic Drugs; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine