ED50 AP Block Predictions for Phenyl Substituted and Unsubstituted n-Alkanols

ED50 AP Block Predictions for Phenyl Substituted and Unsubstituted n-Alkanols A series of n-alkanols and phenyl-substituted n-alkanols (Φ-alkanols) of increasing chain length and phenol were characterized for their ability to block action potentials (APs) in frog sciatic nerves. APs were recorded using the single sucrose-gap method. The degree of AP attenuation when the nerve was exposed to different concentrations of an alcohol was used to construct dose-response curves. The reciprocals of the half-blocking doses (ED50s) were used to obtain a measure of the potency of the alcohols. For n-alkanols and Φ-alkanols, increasing the chain length by the addition of a methylene group increased the potency on average by 3.1 for both groups of alkanols. The addition of a phenyl group caused a potency increase that ranged between the values of 77 and 122. The ED50 for both groups of alkanols could not be solely predicted by the log octanol-water partition coefficient (K OW ). Using linear solvation energy relations (LSER), the log ED50 could be described as a linear combination of the intrinsic (van der Waals) molar volume (V I ), polarity (P), and hydrogen bond acceptor basicity (β) and donor acidity (α). Size alone could not predict the ED50 for both n-alkanols and Φ-alkanols. The results are consistent with the hypothesis that alkanols bind to and interact with Na channels to cause AP block. Phenyl group addition to an alkanol markedly increases the molecule's potency. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

ED50 AP Block Predictions for Phenyl Substituted and Unsubstituted n-Alkanols

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Copyright © Inc. by 2001 Springer-Verlag New York
Life Sciences; Biochemistry, general; Human Physiology
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