Structural Correlates of Anesthetic Potency in Alkyl Alcohols

James Sidie PhDUrsinus College

Eigenmannia virescensTransparent Knife Fish

WEAKLY ELECTRIC FISHCONTINUOUS EOD / PULSE EOD

ELECTRIC ORGAN DISCHARGE (EOD)Eigenmannia virescens

MEDULLARY PACEMAKER NUCLEUSEigenmannia virescens

EXPERIMENTAL CONFIGURATION

EFFECT OF CHAIN LENGTH ON EOD FREQUENCY - 50 ppm

EFFECT OF CHAIN LENGTH ON EOD FREQUENCY - 25ppm

CUBIC SPLINE ANALYSIS - FIRST FOUR MINUTES OF EXPOSURE TO

ALCOHOL

EFFECT OF CHAIN LENGTH ON EOD FREQUENCY - 12.5 ppm

ANESTHETIC POTENCY OF UNSATURATED OCTANOLS

MOLECULAR MODELLING OF UNSATURATED OCTANOLS

EFFECT OF TEMPERATURE (25C/30C) ON OCTANOL EOD DEPRESSION

EFFECT OF PKC INHIBITOR (CALBIOCHEM Go6983) ON OCTANOL

CONCLUSIONS

• ANESTHETIC POTENCY OF ALKYL ALCOHOLS AT 12.5/25/50 PPM IS POSITIVELY CORRELATED WITH CHAIN LENGTH UP TO 10 CARBONS

• THE MORE TERMINAL THE POSITION OF THE -OH GROUP, THE GREATER THE POTENCY OF THE OCTANOL ISOMER

• THE PRESENCE OF A DOUBLE BOND DECREASES ANESTHETIC POTENCY AS A FUNCTION OF BOND POSITION

• PENTADECAFLUOROOCTANOL HAS NO ANESTHETIC EFFECT

ACKNOWLEDGEMENTSDR. ERIC WILLIAMSEN DEPT. OF CHEMISTRY

JUDY LYTLE

ANGELO LEPORE

BETH HOLLOWAY

JENNIFER DERUYTER

HHMI

MERCK / AAAS

MOLECULAR MODELLING OF 1,8 OCTANEDIOL

TRENDS IN PHYSIOLOGICAL AND CONCENTRATION DATA

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C6H13OH C7H15OH C8H17OH C9H19OH C10H21OH

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anol Concntration Data

Physiological Data

GC CONCENTRATION MEASUREMENTS FOR GOLDFISH

Percent Alcohol Concentration of Initial Concentrationl for Goldfish

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Number of Carbons in Alcohol Chain

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