PMID- 32875347
OWN - NLM
STAT- MEDLINE
DCOM- 20210203
LR  - 20211203
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 237
IP  - 12
DP  - 2020 Dec
TI  - The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the 
      effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male 
      rats.
PG  - 3703-3714
LID - 10.1007/s00213-020-05648-z [doi]
AB  - RATIONALE: The nonmedical use of new psychoactive substances (NPS) is a worldwide 
      public health concern. The so-called "benzofury" compounds, 
      5-(2-aminopropyl)benzofuran (5-APB) and 6-(2-aminopropyl)benzofuran (6-APB), are 
      NPS with stimulant-like properties in human users. These substances are known to 
      interact with monoamine transporters and 5-HT receptors in transfected cells, but 
      less is known about their effects in animal models. METHODS: Here, we used in 
      vitro monoamine transporter assays in rat brain synaptosomes to characterize the 
      effects of 5-APB and 6-APB, together with their N-methyl derivatives 5-MAPB and 
      6-MAPB, in comparison with 3,4-methylenedioxyamphetamine (MDA) and 
      3,4-methylenedioxymethamphetamine (MDMA). In vivo neurochemical and behavioral 
      effects of 5-APB (0.3 and 1.0 mg/kg, i.v.) and 6-APB (0.3 and 1.0 mg/kg, i.v.) 
      were assessed in comparison with MDA (1.0 and 3.0 mg/kg, i.v.) using 
      microdialysis sampling in the nucleus accumbens of conscious male rats. RESULTS: 
      All four benzofuran derivatives were substrate-type releasers at dopamine 
      transporters (DAT), norepinephrine transporters (NET), and serotonin transporters 
      (SERT) with nanomolar potencies, similar to the profile of effects produced by 
      MDA and MDMA. However, the benzofurans were at least threefold more potent than 
      MDA and MDMA at evoking transporter-mediated release. Like MDA, both benzofurans 
      induced dose-related elevations in extracellular dopamine and serotonin in the 
      brain, but benzofurans were more potent than MDA. The benzofuran derivatives also 
      induced profound behavioral activation characterized by forward locomotion which 
      lasted for at least 2 h post-injection. CONCLUSIONS: Overall, benzofurans are 
      more potent than MDA in vitro and in vivo, producing sustained stimulant-like 
      effects in rats. These data suggest that benzofuran-type compounds may have abuse 
      liability and could pose risks for adverse effects, especially if used in 
      conjunction with abused drugs or medications which enhance monoamine transmission 
      in the brain.
FAU - Brandt, Simon D
AU  - Brandt SD
AD  - School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, 
      Byrom Street, L3 3AF, Liverpool, UK.
FAU - Walters, Hailey M
AU  - Walters HM
AD  - Designer Drug Research Unit, Intramural Research Program, National Institute on 
      Drug Abuse, National Institutes of Health, 333 Cassell Drive, Suite 4400, 
      Baltimore, MD, 21224, USA.
FAU - Partilla, John S
AU  - Partilla JS
AD  - Designer Drug Research Unit, Intramural Research Program, National Institute on 
      Drug Abuse, National Institutes of Health, 333 Cassell Drive, Suite 4400, 
      Baltimore, MD, 21224, USA.
FAU - Blough, Bruce E
AU  - Blough BE
AD  - Center for Drug Discovery, RTI International, 3040 Cornwallis Rd, Research 
      Triangle Park, NC, 27709, USA.
FAU - Kavanagh, Pierce V
AU  - Kavanagh PV
AD  - Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre 
      for Health Sciences, St. James Hospital, Dublin, 8, Ireland.
FAU - Baumann, Michael H
AU  - Baumann MH
AUID- ORCID: 0000-0001-7758-1470
AD  - Designer Drug Research Unit, Intramural Research Program, National Institute on 
      Drug Abuse, National Institutes of Health, 333 Cassell Drive, Suite 4400, 
      Baltimore, MD, 21224, USA. mbaumann@mail.nih.gov.
LA  - eng
GR  - K23 DA000523/DA/NIDA NIH HHS/United States
GR  - Z01 DA000523/ImNIH/Intramural NIH HHS/United States
GR  - ZIA DA000523/ImNIH/Intramural NIH HHS/United States
GR  - DA 000523/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20200901
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Benzofurans)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Norepinephrine Plasma Membrane Transport Proteins)
RN  - 0 (Propylamines)
RN  - 0 (Psychotropic Drugs)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 285VE60914 (6-(2-aminopropyl)benzofuran)
RN  - 2M3825704H (5-(2-aminopropyl)benzofuran)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/chemistry/*pharmacology
MH  - Animals
MH  - Benzofurans/chemistry/*pharmacology
MH  - Dopamine Plasma Membrane Transport Proteins/agonists/*metabolism
MH  - Male
MH  - Norepinephrine Plasma Membrane Transport Proteins/agonists/*metabolism
MH  - Propylamines/chemistry/*pharmacology
MH  - Psychotropic Drugs/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin Plasma Membrane Transport Proteins/agonists/*metabolism
PMC - PMC7686291
MID - NIHMS1625695
OTO - NOTNLM
OT  - Benzofury
OT  - Designer drugs
OT  - Locomotor activity
OT  - MDMA, MDA
OT  - Microdialysis
OT  - Monoamine transporter
OT  - Release
OT  - Synthetic stimulants
COIS- Conflict of interest The authors declare that they have no conflict of interest.
EDAT- 2020/09/03 06:00
MHDA- 2021/02/04 06:00
PMCR- 2021/12/01
CRDT- 2020/09/03 06:00
PHST- 2020/05/27 00:00 [received]
PHST- 2020/08/20 00:00 [accepted]
PHST- 2020/09/03 06:00 [pubmed]
PHST- 2021/02/04 06:00 [medline]
PHST- 2020/09/03 06:00 [entrez]
PHST- 2021/12/01 00:00 [pmc-release]
AID - 10.1007/s00213-020-05648-z [pii]
AID - 10.1007/s00213-020-05648-z [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2020 Dec;237(12):3703-3714. doi: 
      10.1007/s00213-020-05648-z. Epub 2020 Sep 1.