PMID- 30904940
OWN - NLM
STAT- MEDLINE
DCOM- 20190827
LR  - 20210109
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 236
IP  - 3
DP  - 2019 Mar
TI  - 2-Aminoindan and its ring-substituted derivatives interact with plasma membrane 
      monoamine transporters and alpha(2)-adrenergic receptors.
PG  - 989-999
LID - 10.1007/s00213-019-05207-1 [doi]
AB  - RATIONALE: Over the last decade, many new psychostimulant analogues have appeared 
      on the recreational drug market and most are derivatives of amphetamine or 
      cathinone. Another class of designer drugs is derived from the 2-aminoindan 
      structural template. Several members of this class, including the parent compound 
      2-aminoindan (2-AI), have been sold as designer drugs. Another aminoindan 
      derivative, 5-methoxy-2-aminoindan (5-MeO-AI or MEAI), is the active ingredient 
      in a product marketed online as an alcohol substitute. METHODS: Here, we tested 
      2-AI and its ring-substituted derivatives 5-MeO-AI, 
      5-methoxy-6-methyl-2-aminoindan (MMAI), and 5,6-methylenedioxy-2-aminoindan 
      (MDAI) for their abilities to interact with plasma membrane monoamine 
      transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT). We 
      also compared the binding affinities of the aminoindans at 29 receptor and 
      transporter binding sites. RESULTS: 2-AI was a selective substrate for NET and 
      DAT. Ring substitution increased potency at SERT while reducing potency at DAT 
      and NET. MDAI was moderately selective for SERT and NET, with tenfold weaker 
      effects on DAT. 5-MeO-AI exhibited some selectivity for SERT, having sixfold 
      lower potency at NET and 20-fold lower potency at DAT. MMAI was highly selective 
      for SERT, with 100-fold lower potency at NET and DAT. The aminoindans had 
      relatively high affinity for alpha(2)-adrenoceptor subtypes. 2-AI had particularly 
      high affinity for alpha(2C) receptors (K(i) = 41 nM) and slightly lower affinity for 
      the alpha(2A) (K(i) = 134 nM) and alpha(2B) (K(i) = 211 nM) subtypes. 5-MeO-AI and MMAI 
      also had moderate affinity for the 5-HT(2B) receptor. CONCLUSIONS: 2-AI is 
      predicted to have (+)-amphetamine-like effects and abuse potential whereas the 
      ring-substituted derivatives may produce 3,4-methylenedioxymethamphetamine 
      (MDMA)-like effects but with less abuse liability.
FAU - Halberstadt, Adam L
AU  - Halberstadt AL
AD  - Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, 
      La Jolla, CA, 92093-0804, USA. ahalberstadt@ucsd.edu.
AD  - Research Service, VA San Diego Healthcare System, 3350 La Jolla Village Dr., San 
      Diego, CA, 92161, USA. ahalberstadt@ucsd.edu.
FAU - Brandt, Simon D
AU  - Brandt SD
AD  - School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, 
      Byrom Street, Liverpool, L3 3AF, UK.
FAU - Walther, Donna
AU  - Walther D
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  - K23 DA000523/DA/NIDA NIH HHS/United States
GR  - R01 DA041336/DA/NIDA NIH HHS/United States
GR  - Z01 DA000523/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20190323
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Indans)
RN  - 0 (Norepinephrine Plasma Membrane Transport Proteins)
RN  - 0 (Receptors, Adrenergic, alpha-2)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - 1P810SQ3EY (2-aminoindan)
RN  - 333DO1RDJY (Serotonin)
RN  - CK833KGX7E (Amphetamine)
RN  - VTD58H1Z2X (Dopamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Amphetamine/metabolism
MH  - Animals
MH  - Cell Membrane/*metabolism
MH  - Dopamine/metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/*metabolism
MH  - Humans
MH  - Indans/chemistry/*metabolism
MH  - Male
MH  - Norepinephrine/metabolism
MH  - Norepinephrine Plasma Membrane Transport Proteins/*metabolism
MH  - Protein Binding/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Adrenergic, alpha-2/*metabolism
MH  - Serotonin/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/*metabolism
MH  - Vesicular Monoamine Transport Proteins/metabolism
PMC - PMC6848746
MID - NIHMS1053818
OTO - NOTNLM
OT  - Analgesia
OT  - Binding
OT  - Dopamine
OT  - MEAI
OT  - Norepinephrine
OT  - Serotonin
OT  - Stimulant
OT  - Synaptosomes
COIS- Conflict of interest: The authors have no conflict of interest, financial or 
      otherwise, to declare.
EDAT- 2019/03/25 06:00
MHDA- 2019/08/28 06:00
PMCR- 2020/03/23
CRDT- 2019/03/25 06:00
PHST- 2018/07/26 00:00 [received]
PHST- 2019/02/25 00:00 [accepted]
PHST- 2019/03/25 06:00 [pubmed]
PHST- 2019/08/28 06:00 [medline]
PHST- 2019/03/25 06:00 [entrez]
PHST- 2020/03/23 00:00 [pmc-release]
AID - 10.1007/s00213-019-05207-1 [pii]
AID - 10.1007/s00213-019-05207-1 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2019 Mar;236(3):989-999. doi: 
      10.1007/s00213-019-05207-1. Epub 2019 Mar 23.