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
0
20
40
60
80
100
120
C6H13OH C7H15OH C8H17OH C9H19OH C10H21OH
Perc
ent o
f Nor
mal
ized
Val
ues
at
Dec
anol Concntration Data
Physiological Data
GC CONCENTRATION MEASUREMENTS FOR GOLDFISH
Percent Alcohol Concentration of Initial Concentrationl for Goldfish
0
20
40
60
80
100
5 6 7 8 9 10
Number of Carbons in Alcohol Chain
Ave
rage
Per
cent
of I
nitia
l C
once
ntra
tion