Anesthetic potency of two novel synthetic polyhydric alkanols longer than the n-alkanol cutoff: evidence for a bilayer-mediated mechanism of anesthesia?

J Med Chem. 2005 Jun 16;48(12):4172-6. doi: 10.1021/jm049459k.

Abstract

The polyhydroxyalkanes 1,6,11,16-hexadecanetetraol (1) and 2,7,12,17-octadecanetetraol (2) were synthesized utilizing the thiophene ring as a scaffold to affix the hydroxyalkyl chains by lithiation of the acidic alpha-hydrogens and subsequent desulfurization. Both compounds exhibited significant anesthetic potency, individually and in additivity studies with hexanol, using immobility in tadpoles as the phenotypic endpoint. These results, which contradict a protein-binding mechanism in which cutoff results from steric hindrance, are consistent with recent predictions of a membrane-mediated mechanism involving the lateral pressure profile.

MeSH terms

  • Anesthetics, General / chemical synthesis*
  • Anesthetics, General / chemistry
  • Anesthetics, General / pharmacology*
  • Animals
  • Fatty Alcohols / chemical synthesis
  • Fatty Alcohols / chemistry
  • Fatty Alcohols / pharmacology*
  • Hexanols / chemistry*
  • Larva / drug effects
  • Lipid Bilayers / metabolism*
  • Motor Activity / drug effects
  • Solubility
  • Xenopus

Substances

  • 1,6,11,16-hexadecanetetraol
  • Anesthetics, General
  • Fatty Alcohols
  • Hexanols
  • Lipid Bilayers
  • 1-hexanol