Effect of ring-constrained phenylpropyloxyethylamines on sigma receptors

Bioorg Med Chem. 2013 Sep 1;21(17):4923-7. doi: 10.1016/j.bmc.2013.06.068. Epub 2013 Jul 11.

Abstract

A series of ring-constrained phenylpropyloxyethylamines, partial opioid structure analogs and derivatives of a previously studied sigma (σ) receptor ligand, was synthesized and evaluated at σ and opioid receptors for receptor selectivity. The results of this study identified several compounds with nanomolar affinity at both σ receptor subtypes. Compounds 6 and 9 had the highest selectivity for both σ receptor subtypes, compared to μ opioid receptors. In addition, compounds 6 and 9 significantly reduced the convulsive effects of cocaine in mice, which would be consistent with antagonism of σ receptors.

Keywords: Antagonists; Opioid; Phenylpropyloxyethylaminesl; Sigma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cocaine / chemistry
  • Cocaine / toxicity
  • Convulsants / chemistry
  • Convulsants / metabolism
  • Convulsants / therapeutic use
  • Cyclohexanols / chemistry*
  • Cyclohexanols / metabolism
  • Cyclohexanols / therapeutic use
  • Ethylamines / chemistry*
  • Ethylamines / metabolism
  • Ethylamines / therapeutic use
  • Mice
  • Phenethylamines / chemistry*
  • Phenethylamines / metabolism
  • Phenethylamines / therapeutic use
  • Propylamines / chemistry*
  • Propylamines / metabolism
  • Propylamines / therapeutic use
  • Protein Binding
  • Receptors, sigma / antagonists & inhibitors*
  • Receptors, sigma / metabolism
  • Seizures / chemically induced
  • Seizures / drug therapy

Substances

  • 2-(methyl(3-phenylpropyl)amino)cyclohexanol
  • 2-(methyl(phenethyl)amino)cyclohexanol
  • Convulsants
  • Cyclohexanols
  • Ethylamines
  • Phenethylamines
  • Propylamines
  • Receptors, sigma
  • Cocaine