PMID- 27650729
OWN - NLM
STAT- MEDLINE
DCOM- 20170221
LR  - 20181113
IS  - 1432-1912 (Electronic)
IS  - 0028-1298 (Linking)
VI  - 390
IP  - 1
DP  - 2017 Jan
TI  - Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.
PG  - 15-24
LID - 10.1007/s00210-016-1297-4 [doi]
AB  - 3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in 
      the treatment of post-traumatic stress disorder (PTSD) in numerous clinical 
      trials. In the present study, we have characterized the neurochemical binding 
      profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 
      5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 
      1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue 
      (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were 
      screened as potential second-generation anti-PTSD drugs, against a battery of 
      human and non-human receptors, transporters, and enzymes, and their potencies as 
      5-HT(2) receptor agonist and monoamine uptake inhibitors determined. All MDMA 
      analogues displayed high binding affinities for 5-HT(2a,b,c) and NE(alpha2) 
      receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB 
      revealed significant agonist activity at the 5-HT(2a,b,c) receptors, while 
      6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT(2c) 
      receptor. There was a lack of correlation between the results of functional 
      uptake and the monoamine transporter binding assay. MDMA analogues emerged as 
      potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable 
      pharmacological profile, it was further subjected to IC(50) determination for 
      monoamine transporters. Overall, all MDMA analogues displayed higher monoamine 
      receptor/transporter binding affinities and agonist activity at the 5-HT(2a,c) 
      receptors as compared to MDMA.
FAU - Shimshoni, Jakob A
AU  - Shimshoni JA
AD  - Department of Toxicology, Kimron Veterinary Institute, Bet Dagan, Israel. 
      jakobs@moag.gov.il.
FAU - Winkler, Ilan
AU  - Winkler I
AD  - Pharmaseed Ltd, Ness Ziona, Israel.
FAU - Golan, Ezekiel
AU  - Golan E
AD  - BSC BV Company, Veemarkt 61, Amsterdam, Netherlands.
FAU - Nutt, David
AU  - Nutt D
AD  - Neuropsychopharmacology Unit, Imperial College London, London, UK.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20160920
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Benzofurans)
RN  - 0 (Indoles)
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - 0 (Neurotransmitter Uptake Inhibitors)
RN  - 0 (Receptors, Serotonin, 5-HT2)
RN  - 0 (Serotonin 5-HT2 Receptor Agonists)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Benzofurans/chemistry/*metabolism/pharmacology
MH  - Binding Sites
MH  - Catechol O-Methyltransferase/chemistry/metabolism
MH  - Humans
MH  - Indoles/chemistry/*metabolism/pharmacology
MH  - Monoamine Oxidase/chemistry/metabolism
MH  - Monoamine Oxidase Inhibitors/chemistry/metabolism/pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/chemistry/*metabolism/pharmacology
MH  - Neurotransmitter Uptake Inhibitors/chemistry/*metabolism/pharmacology
MH  - Protein Binding
MH  - Protein Conformation
MH  - Radioligand Assay
MH  - Receptors, Serotonin, 5-HT2/chemistry/drug effects/*metabolism
MH  - Serotonin 5-HT2 Receptor Agonists/chemistry/*metabolism/pharmacology
MH  - Stress Disorders, Post-Traumatic/*drug therapy/metabolism
MH  - Structure-Activity Relationship
MH  - Tyrosine 3-Monooxygenase/chemistry/metabolism
MH  - Vesicular Monoamine Transport Proteins/antagonists & 
      inhibitors/chemistry/*metabolism
OTO - NOTNLM
OT  - 3,4-Methylenedioxy-N-methylamphetamine (MDMA)
OT  - MDMA analogues
OT  - Monoamine receptors
OT  - Monoamine transporters
OT  - Neurochemical profile
EDAT- 2016/09/22 06:00
MHDA- 2017/02/22 06:00
CRDT- 2016/09/22 06:00
PHST- 2016/02/14 00:00 [received]
PHST- 2016/09/02 00:00 [accepted]
PHST- 2016/09/22 06:00 [pubmed]
PHST- 2017/02/22 06:00 [medline]
PHST- 2016/09/22 06:00 [entrez]
AID - 10.1007/s00210-016-1297-4 [pii]
AID - 10.1007/s00210-016-1297-4 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2017 Jan;390(1):15-24. doi: 
      10.1007/s00210-016-1297-4. Epub 2016 Sep 20.