PMID- 26362361
OWN - NLM
STAT- MEDLINE
DCOM- 20160922
LR  - 20190117
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 101
DP  - 2016 Feb
TI  - The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 
      6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain 
      tissue.
PG  - 68-75
LID - S0028-3908(15)30095-2 [pii]
LID - 10.1016/j.neuropharm.2015.09.004 [doi]
AB  - In recent years, use of psychoactive synthetic stimulants has grown rapidly. 
      5-(2-Aminopropyl)indole (5-IT) is a synthetic drug associated with a number of 
      fatalities, that appears to be one of the newest 
      3,4-methylenedioxymethamphetamine (MDMA) replacements. Here, the 
      monoamine-releasing properties of 5-IT, its structural isomer 
      6-(2-aminopropyl)indole (6-IT), and MDMA were compared using in vitro release 
      assays at transporters for dopamine (DAT), norepinephrine (NET), and serotonin 
      (SERT) in rat brain synaptosomes. In vivo pharmacology was assessed by locomotor 
      activity and a functional observational battery (FOB) in mice. 5-IT and 6-IT were 
      potent substrates at DAT, NET, and SERT. In contrast with the non-selective 
      releasing properties of MDMA, 5-IT displayed greater potency for release at DAT 
      over SERT, while 6-IT displayed greater potency for release at SERT over DAT. 
      5-IT produced locomotor stimulation and typical stimulant effects in the FOB 
      similar to those produced by MDMA. Conversely, 6-IT increased behaviors 
      associated with 5-HT toxicity. 5-IT likely has high abuse potential, which may be 
      somewhat diminished by its slow onset of in vivo effects, whereas 6-IT may have 
      low abuse liability, but enhanced risk for adverse effects. Results indicate that 
      subtle differences in the chemical structure of transporter ligands can have 
      profound effects on biological activity. The potent monoamine-releasing actions 
      of 5-IT, coupled with its known inhibition of MAO A, could underlie its dangerous 
      effects when administered alone, and in combination with other monoaminergic 
      drugs or medications. Consequently, 5-IT and related compounds may pose 
      substantial risk for abuse and serious adverse effects in human users.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Marusich, Julie A
AU  - Marusich JA
AD  - Center for Drug Discovery, RTI International, 3040 Cornwallis Rd, Research 
      Triangle Park, NC 27709, USA. Electronic address: jmarusich@rti.org.
FAU - Antonazzo, Kateland R
AU  - Antonazzo KR
AD  - Center for Drug Discovery, RTI International, 3040 Cornwallis Rd, Research 
      Triangle Park, NC 27709, 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 - Brandt, Simon D
AU  - Brandt SD
AD  - School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, 
      Byrom Street, L3 3AF, Liverpool, UK.
FAU - Kavanagh, Pierce V
AU  - Kavanagh PV
AD  - Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre 
      for Health Sciences, St. James's Hospital, Dublin 8, Ireland.
FAU - Partilla, John S
AU  - Partilla JS
AD  - Designer Drug Research Unit, Intramural Research Program, National Institute on 
      Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
FAU - Baumann, Michael H
AU  - Baumann MH
AD  - Designer Drug Research Unit, Intramural Research Program, National Institute on 
      Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
LA  - eng
GR  - R01 DA012970/DA/NIDA NIH HHS/United States
GR  - DA12970/DA/NIDA NIH HHS/United States
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150908
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Indoles)
RN  - 0 (Neurotransmitter Transport Proteins)
RN  - 10028-17-8 (Tritium)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - W98BOE73HH (5-(2-aminopropyl)indole)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/pharmacology
MH  - Animals
MH  - Brain/*drug effects
MH  - Central Nervous System Stimulants/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - In Vitro Techniques
MH  - Indoles/*pharmacology
MH  - Male
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - Neurotransmitter Transport Proteins/genetics/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/pharmacokinetics
MH  - Time Factors
MH  - Tritium/pharmacokinetics
PMC - PMC4681602
MID - NIHMS725542
OTO - NOTNLM
OT  - 3,4-Methylenedioxymethamphetamine (MDMA)
OT  - 5-(2-Aminopropyl)indole (5-IT)
OT  - 6-(2-Aminopropyl)indole (6-IT)
OT  - Locomotor activity
OT  - Monoamine releaser
OT  - Synthetic stimulants
COIS- Conflicts of Interest The authors have no conflicts of interest.
EDAT- 2015/09/13 06:00
MHDA- 2016/09/23 06:00
PMCR- 2017/02/01
CRDT- 2015/09/13 06:00
PHST- 2015/07/08 00:00 [received]
PHST- 2015/08/24 00:00 [revised]
PHST- 2015/09/02 00:00 [accepted]
PHST- 2015/09/13 06:00 [entrez]
PHST- 2015/09/13 06:00 [pubmed]
PHST- 2016/09/23 06:00 [medline]
PHST- 2017/02/01 00:00 [pmc-release]
AID - S0028-3908(15)30095-2 [pii]
AID - 10.1016/j.neuropharm.2015.09.004 [doi]
PST - ppublish
SO  - Neuropharmacology. 2016 Feb;101:68-75. doi: 10.1016/j.neuropharm.2015.09.004. 
      Epub 2015 Sep 8.