PMID- 25765500
OWN - NLM
STAT- MEDLINE
DCOM- 20160407
LR  - 20240323
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 172
IP  - 13
DP  - 2015 Jul
TI  - Pharmacological profile of novel psychoactive benzofurans.
PG  - 3412-25
LID - 10.1111/bph.13128 [doi]
AB  - BACKGROUND AND PURPOSE: Benzofurans are newly used psychoactive substances, but 
      their pharmacology is unknown. The aim of the present study was to 
      pharmacologically characterize benzofurans in vitro. EXPERIMENTAL APPROACH: 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. KEY 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 AND IMPLICATIONS: 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.
CI  - (c) 2015 The British Pharmacological Society.
FAU - Rickli, Anna
AU  - Rickli A
AD  - Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, 
      Department of Biomedicine, University Hospital Basel and University of Basel, 
      Basel, Switzerland.
FAU - Kopf, Simone
AU  - Kopf S
AD  - Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, 
      Department of Biomedicine, University Hospital Basel and University of Basel, 
      Basel, Switzerland.
FAU - Hoener, Marius C
AU  - Hoener MC
AD  - Neuroscience Research, pRED, Roche Innovation Center Basel, F. Hoffmann-La Roche 
      Ltd, Basel, Switzerland.
FAU - Liechti, Matthias E
AU  - Liechti ME
AD  - Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, 
      Department of Biomedicine, University Hospital Basel and University of Basel, 
      Basel, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150424
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Benzofurans)
RN  - 0 (Norepinephrine Plasma Membrane Transport Proteins)
RN  - 0 (Psychotropic Drugs)
RN  - 0 (Receptors, Dopamine)
RN  - 0 (Receptors, Serotonin)
RN  - 333DO1RDJY (Serotonin)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Benzofurans/*pharmacology
MH  - Cell Survival/drug effects
MH  - Dopamine/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Norepinephrine/metabolism
MH  - Norepinephrine Plasma Membrane Transport Proteins/metabolism
MH  - Psychotropic Drugs/*pharmacology
MH  - Receptors, Dopamine/metabolism
MH  - Receptors, Serotonin/metabolism
MH  - Serotonin/metabolism
PMC - PMC4500375
EDAT- 2015/03/15 06:00
MHDA- 2016/04/08 06:00
PMCR- 2016/07/01
CRDT- 2015/03/14 06:00
PHST- 2014/12/23 00:00 [received]
PHST- 2015/02/06 00:00 [revised]
PHST- 2015/03/09 00:00 [accepted]
PHST- 2015/03/14 06:00 [entrez]
PHST- 2015/03/15 06:00 [pubmed]
PHST- 2016/04/08 06:00 [medline]
PHST- 2016/07/01 00:00 [pmc-release]
AID - 10.1111/bph.13128 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2015 Jul;172(13):3412-25. doi: 10.1111/bph.13128. Epub 2015 Apr 
      24.