N -Benzyl-5-methoxytryptamines as Potent Serotonin 5-HT 2 Receptor Family Agonists and Comparison with a Series of Phenethylamine Analogues

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Nichols, David E.
    • University of North Carolina at Chapel Hill
  • Sassano, M. Flori
    • University of North Carolina at Chapel Hill
  • Halberstadt, Adam L.
    • Other Affiliation: University of California, San Diego
  • Klein, Landon M.
    • Other Affiliation: University of California, San Diego
  • Brandt, Simon D.
    • Other Affiliation: Liverpool John Moores University
  • Elliott, Simon P.
    • Other Affiliation: Alere Forensics
  • Fiedler, Wolfgang J.
Abstract
  • A series of N-benzylated-5-methoxytryptamine analogues was prepared and investigated, with special emphasis on substituents in the meta position of the benzyl group. A parallel series of several N-benzylated analogues of 2,5-dimethoxy-4-iodophenethylamine (2C-I) also was included for comparison of the two major templates (i.e., tryptamine and phenethylamine). A broad affinity screen at serotonin receptors showed that most of the compounds had the highest affinity at the 5-HT2 family receptors. Substitution at the para position of the benzyl group resulted in reduced affinity, whereas substitution in either the ortho or the meta position enhanced affinity. In general, introduction of a large lipophilic group improved affinity, whereas functional activity often followed the opposite trend. Tests of the compounds for functional activity utilized intracellular Ca2+ mobilization. Function was measured at the human 5-HT2A, 5-HT2B, and 5-HT2C receptors, as well as at the rat 5-HT2A and 5-HT2C receptors. There was no general correlation between affinity and function. Several of the tryptamine congeners were very potent functionally (EC50 values from 7.6 to 63 nM), but most were partial agonists. Tests in the mouse head twitch assay revealed that many of the compounds induced the head twitch and that there was a significant correlation between this behavior and functional potency at the rat 5-HT2A receptor.
Date of publication
Keyword
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • ACS Chemical Neuroscience
Journal volume
  • 6
Journal issue
  • 7
Language
  • English
ISSN
  • 1948-7193

Relations

Parents:

This work has no parents.

Items

Thumbnail Title Date Uploaded Visibility Actions
file details PubMedCentral-PMC4505863.pdf October 28, 2020 Public Download