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

Volumn 48, Issue 12, 2005, Pages 4172-4176

  Mohr, Justin T ^a   Gribble, Gordon W ^a   Lin, Susan S ^b   Eckenhoff, Roderic G ^b   Cantor, Robert S ^a,c  

^a Dartmouth College   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

1,6,11,16 HEXADECANETETRAOL; 2,7,12,17 OCTADECANETETRAOL; ALKANE DERIVATIVE; ALKANOL; ANESTHETIC AGENT; HEXANOL; UNCLASSIFIED DRUG;

ANESTHESIA; ANIMAL EXPERIMENT; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DESULFURIZATION; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; IMMOBILIZATION; LITHIATION; NONHUMAN; PHENOTYPE; PROTEIN BINDING; TADPOLE;

ANESTHETICS, GENERAL; ANIMALS; FATTY ALCOHOLS; HEXANOLS; LARVA; LIPID BILAYERS; MOTOR ACTIVITY; SOLUBILITY; XENOPUS;

EID: 20444391306     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049459k     Document Type: Article

References (12)

1. Janoff, A. S.; Miller, K. W. A Critical Assessment of the Lipid Theories of General Anaesthetic Action. In Biological Membranes; Chapman, D., Ed.; Academic Press: London, 1982; Vol. 4, pp 417-476.
2. Wick, M. J.; Mihic, S. J.; Ueno, S.; Mascia, M. P.; Trudell, J. R.; Brozowski, S. J.; Ye, Q.; Harrison, N. L.; Harris, R. A. Mutations of γ-aminobutyric acid and glycine receptors change alcohol cutoff: Evidence for an alcohol receptor? Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 6504-6509.
3. Jenkins, A.; Greenblatt, E. P.; Faulkner, H. J.; Bertaccini, E.; Light, A.; Lin, A.; Andreasen, A.; Viner, A.; Trudell, J. R.; Harrison, N. L. Evidence for a common binding cavity for three general anesthetics within the GABAA receptor. J. Neurosci. 2001, 21, 1-4.
4. Eckenhoff, R. G.; Tanner, J. W.; Johansson, J. S. Steric hindrance is not required for n-alkanol cutoff in soluble proteins. Mol. Pharmacol. 1999, 56, 414-418.
5. Cantor, R. S. Breaking the Meyer-Overton rule: Predicted effects of varying stiffness and interfacial activity on the intrinsic potency of anesthetics. Biophys. J. 2001, 80, 2284-2297.
6. Peoples, R. W.; Ren, H. Inhibition of N-methyl-D-aspartate receptors by straight-chain diols: Implications for the mechanism of the alcohol cutoff effect. Mol. Pharmacol. 2002, 61, 169-176.
7. Meyers, A. I. Heterocycles in Organic Synthesis; John Wiley: New York, 1974; pp 15-20, 228-231.
8. Krishna, P. R.; Lavanya, B.; Ilangovan, A.; Sharma, G. V. M. Stereoselective synthesis of C-alkyl and functionalised C-alkyl glycosides using "thiophene" as a masked C-4 synthon. Tetrahedron: Asymmetry 2000, 11, 4463-4472.
9. Yang, S.-M.; Nandy, S. K.; Selvakumar, A. R.; Fang, J.-M. Distant functionalization via incorporation of thiophene moieties in electrophilic reactions promoted by samarium diiodide. Org. Lett. 2000, 2, 3719-3721.
10. Vaitiekunas, A.; Nord, F. F. Studies on the chemistry of heterocyclics. XXV. Investigations on diacetylenes and diacetylenic glycols in the thiophene series. J. Am. Chem. Soc. 1954, 76, 2733-2736.
11. Alifimoff, J. K.; Firestone, L. L.; Miller, K. W. Anaesthetic potencies of primary alkanols: implications for the molecular dimensions of the anaesthetic site. Br. J. Pharmacol. 1989, 96, 9-16.
12. Cole, D.; Kalichman, M.; Shapiro, H.; Eger, E. I., II. Does 1 + 1 = 2? A continuing debate. Anesth. Analg. 1990, 70, 126-127.