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Correlation of parachor with anesthetic potency
Life Sciences Vol . 3, pp . 1131-1134, 1964. Pergamon Press, Inc . Printed in the United States.
CORRELATION OF PARACHOR WITH ANESTHETIC POTENCY Richard H . Adamson Laboratory of Chemical Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
(Received 22 June 1964) VARIOUS theories have been proposed for the mechanism of action of anesthetic agents .
Cellular changes in lipid solubility, surface tension, adsorption,
permeability, protein coagulation, viscosity, oxidation, and respiratory enzymes are among the mechanisms proposed (1) .
Since the demonstration that
the chemically inert gas xenon was an anesthetic agent for man at atmospheric pressure (2)
several new theories of anesthesia have been proposed .
Although
several chemical compounds of xenon (and radon) have been reported xenon is incapable of forming ionic, hydrogen, or co-valent bonds with other atoms under physiological conditions .
This fact restricts all postulated mechanisms of
inert gas anesthesia to the physical level of molecular interaction (3) . Ferguson and Mullins have proposed a thermodynamic approach,
in eluci-
dating a mechanism of action and Wulf and Featherstone have related molecular volume and van der Waals constants to anesthetic potency (3) .
Pauling compared
the dissociation pressures of the hydrates of anesthetic gases and the partial pressures of anesthetics necessary for narcosis and showed that they were both related to molar refraction (4) .
Parachor is a physico-chemical constant
dependent on constitution of the molecule and related to molecular volume . This paper is concerned with the correlations of parachor and anesthetic potency and re-emphasizes the probable importance of molecular volume in determining anesthetic potency .
1132
CORRELATION OF PARACHOR
Vol . 3, No . 10
Methods Parachor values of the anesthetic agents were calculated using atomic and structural parachors (Table 1)
from Sugden (5) .
For example,
the calculation
TABLE 1 Atomic and Structural Parachors
C = 4 .8
Double bond = 23 .2
H = 17 .1
Triple bond = 46 .6
N = 12 .5
3 membered ring = 16 .7
0 = 20 .0
Re
=
91
C1 = 54 .3
Kr
=
68
F = 25 .7
A
=
54
Br = 68 .0
He
=
20 .5
of parachor for chloroform (CHC1 3 ) would be the sum of 1 X 4 .8 (carbon), 1 X 17 .1
(hydrogen),
3 R 54 .3 (chlorine) giving a total of 184 .8 .
The potency
of the anesthetic agents was estYmated from published values of inspired concentrations necessary for deep anesthesia (third stage - second plane or lower) (1,6) . Results and Discussion Parachor correlates well with anesthetic potency .
From Table 2 it is
apparent that generally the greater the calculated parachor value the more potent the anesthetic .
Thus,
fluothane, one of the most potent anesthetic
agents had a parachor value of 226 .1 as contrasted to a parachor value of 81 .1 for nitrous oxide, a weak anesthetic agent .
The non-anesthetic gases krypton,
argon, and helium had parachor values of 68, 54, and 20 .5 respectively,
lower
than that of nitrous oxide . That parachor correlates with anesthetic potency is not surprising . Parachor is a derived function dependent upon the primary properties of molecular weight,
density, and surface tension and is defined by the following
Vol . 3, No. 10
CORRELATION OF PARACHOR
1133
TABLE 2 Parachor Values and Potency of Anesthetic Agents
Agent
Calculated
Effective Inspired
Parachor Value
Concentration
Fluothane
226 .1
0 .5 - 2%
Chloroform
184 .8
1 .3 - 1 .6%
Trifluoroethyl vinyl ether
225 .0
1 .3 - 5%
Diethyl Ether
210 .2
3 .5 - 4 .5%
Divinyl Ether
188 .2
4%
Trichlorethylene
212 .8
5 - 7 .5%
Cyclopropane
133 .7
23 - 40%
Ethylene
101 .2
75 - 80%
Xenon
91
>807
Nitrous Oxide
81 .4
>807<
Krypton
68
non-anesthetic at atmospheric pressure
Argon
54
non-anesthetic at atmospheric pressure
Helium
20 .5
non-anesthetic
formula :
i
P = My4 D-d
where M is the molecular weight, y the surface tension, D the liquid density, and d the vapor density (small compared with D) .
Parachor may be regarded as
a measure of the molecular volumes of liquids at temperatures at which their surface tensions are equal . Molecular volume has been implicated at least indirectly in several theories of anesthesia including lipid solubility, adsorption,
thermodynamic
activity, molecular refraction, and van der Waals constants (3,4) .
The
correlation of parachor and anesthetic potency, while not a "theory" of
1134
Vol. 3, No . 10
CORRELATION OF PARACHOR
anesthesia re-emphasizes the probable importance of molecular volume in determining anesthetic potency . References to
J . ADRIANI, The Pharmacology of Anesthetic Drugs (4th Ed .) . Thomas, Springfield,
Charles C .
(1462) .
2.
S . CULLEN and E . GROSS, Science 113,
3.
R . M . FEATHERSTONE and C . A . MUEHLBAECHER, Pharm . Rev .
4.
L . PAULING, Science 134,
5.
S . SUGDEN,
6.
S . C . CULLEN, Anesthesia (5th Ed .) .
15
580 (1951) . 15,
97
(1963) .
(1961) .
The Parachor and Valency .
George Routledge, London,
(1930) .
Year Book Publishers, Chicago,
(1957) .
CORRELATION OF PARACHOR WITH ANESTHETIC POTENCY Richard H . Adamson Laboratory of Chemical Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
(Received 22 June 1964) VARIOUS theories have been proposed for the mechanism of action of anesthetic agents .
Cellular changes in lipid solubility, surface tension, adsorption,
permeability, protein coagulation, viscosity, oxidation, and respiratory enzymes are among the mechanisms proposed (1) .
Since the demonstration that
the chemically inert gas xenon was an anesthetic agent for man at atmospheric pressure (2)
several new theories of anesthesia have been proposed .
Although
several chemical compounds of xenon (and radon) have been reported xenon is incapable of forming ionic, hydrogen, or co-valent bonds with other atoms under physiological conditions .
This fact restricts all postulated mechanisms of
inert gas anesthesia to the physical level of molecular interaction (3) . Ferguson and Mullins have proposed a thermodynamic approach,
in eluci-
dating a mechanism of action and Wulf and Featherstone have related molecular volume and van der Waals constants to anesthetic potency (3) .
Pauling compared
the dissociation pressures of the hydrates of anesthetic gases and the partial pressures of anesthetics necessary for narcosis and showed that they were both related to molar refraction (4) .
Parachor is a physico-chemical constant
dependent on constitution of the molecule and related to molecular volume . This paper is concerned with the correlations of parachor and anesthetic potency and re-emphasizes the probable importance of molecular volume in determining anesthetic potency .
1132
CORRELATION OF PARACHOR
Vol . 3, No . 10
Methods Parachor values of the anesthetic agents were calculated using atomic and structural parachors (Table 1)
from Sugden (5) .
For example,
the calculation
TABLE 1 Atomic and Structural Parachors
C = 4 .8
Double bond = 23 .2
H = 17 .1
Triple bond = 46 .6
N = 12 .5
3 membered ring = 16 .7
0 = 20 .0
Re
=
91
C1 = 54 .3
Kr
=
68
F = 25 .7
A
=
54
Br = 68 .0
He
=
20 .5
of parachor for chloroform (CHC1 3 ) would be the sum of 1 X 4 .8 (carbon), 1 X 17 .1
(hydrogen),
3 R 54 .3 (chlorine) giving a total of 184 .8 .
The potency
of the anesthetic agents was estYmated from published values of inspired concentrations necessary for deep anesthesia (third stage - second plane or lower) (1,6) . Results and Discussion Parachor correlates well with anesthetic potency .
From Table 2 it is
apparent that generally the greater the calculated parachor value the more potent the anesthetic .
Thus,
fluothane, one of the most potent anesthetic
agents had a parachor value of 226 .1 as contrasted to a parachor value of 81 .1 for nitrous oxide, a weak anesthetic agent .
The non-anesthetic gases krypton,
argon, and helium had parachor values of 68, 54, and 20 .5 respectively,
lower
than that of nitrous oxide . That parachor correlates with anesthetic potency is not surprising . Parachor is a derived function dependent upon the primary properties of molecular weight,
density, and surface tension and is defined by the following
Vol . 3, No. 10
CORRELATION OF PARACHOR
1133
TABLE 2 Parachor Values and Potency of Anesthetic Agents
Agent
Calculated
Effective Inspired
Parachor Value
Concentration
Fluothane
226 .1
0 .5 - 2%
Chloroform
184 .8
1 .3 - 1 .6%
Trifluoroethyl vinyl ether
225 .0
1 .3 - 5%
Diethyl Ether
210 .2
3 .5 - 4 .5%
Divinyl Ether
188 .2
4%
Trichlorethylene
212 .8
5 - 7 .5%
Cyclopropane
133 .7
23 - 40%
Ethylene
101 .2
75 - 80%
Xenon
91
>807
Nitrous Oxide
81 .4
>807<
Krypton
68
non-anesthetic at atmospheric pressure
Argon
54
non-anesthetic at atmospheric pressure
Helium
20 .5
non-anesthetic
formula :
i
P = My4 D-d
where M is the molecular weight, y the surface tension, D the liquid density, and d the vapor density (small compared with D) .
Parachor may be regarded as
a measure of the molecular volumes of liquids at temperatures at which their surface tensions are equal . Molecular volume has been implicated at least indirectly in several theories of anesthesia including lipid solubility, adsorption,
thermodynamic
activity, molecular refraction, and van der Waals constants (3,4) .
The
correlation of parachor and anesthetic potency, while not a "theory" of
1134
Vol. 3, No . 10
CORRELATION OF PARACHOR
anesthesia re-emphasizes the probable importance of molecular volume in determining anesthetic potency . References to
J . ADRIANI, The Pharmacology of Anesthetic Drugs (4th Ed .) . Thomas, Springfield,
Charles C .
(1462) .
2.
S . CULLEN and E . GROSS, Science 113,
3.
R . M . FEATHERSTONE and C . A . MUEHLBAECHER, Pharm . Rev .
4.
L . PAULING, Science 134,
5.
S . SUGDEN,
6.
S . C . CULLEN, Anesthesia (5th Ed .) .
15
580 (1951) . 15,
97
(1963) .
(1961) .
The Parachor and Valency .
George Routledge, London,
(1930) .
Year Book Publishers, Chicago,
(1957) .