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

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

Journal of medicinal chemistry (2005-06-10)
Justin T Mohr, Gordon W Gribble, Susan S Lin, Roderic G Eckenhoff, Robert S Cantor
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.

MATERIALS
Product Number
Brand
Product Description

Supelco
1-Hexanol, analytical standard
Sigma-Aldrich
1-Hexanol, ReagentPlus®, ≥99.5% (GC)
Sigma-Aldrich
Hexyl alcohol, natural, ≥98%, FCC, FG
Sigma-Aldrich
Hexyl alcohol, FCC, FG
Sigma-Aldrich
1-Hexanol, anhydrous, ≥99%
Sigma-Aldrich
1-Hexanol, reagent grade, 98%