THE LOCAL ANESTHETIC PROPERTIES OF PHENYL

METHYL CARBINOL

AXEL M. HJORT AND CHARLES E. KAUFMANN

From the Department of Pharmacology, Yale Univer8ity School of MedicineL

Received for publication January 5, 1920

INTRODUCTION

Benzyl alcohol was described by Macht (1) as having local

anesthetic properties. Rose oil or -phenethylol was shown to
possess similar activities by Hjort and Eagan (2). Phenyl
methyl carbinol or a-phenethylol as will be seen from its struc-
tural formula is a homologue of both of the above mentioned
substances.
H 11011 H
/C% H /C% I /C\1111
HC C-C-OH HC C-C-CIT3 HC C-C-C-OH
II I H II I I II I E1 11
HC OH HC CHH HC CH

H H H
Benzyl alcohol Phenyl methyl Rose oil
carbinol

Phenyl methyl carbinol differs from rose oil only in the position
of the hydroxyl group. The former by having this group in
the a-position possesses an asymmetric carbon atom. It was
expected, therefore, that the a-phenethylol has greater physi-
ological activity than the a-alcohol (3). This surmise, as will
be seen later, held true.

1 This research has been supported by a grant from the Committee on Scientific
Research of the American Medical Association.
129
130 AXEL M. HJORT AND CHARLES E. KAUFMANN

PREPARATION, INCLUDING ITS CHEMICAL AND PHYSICAL PROPERTIES

Phenyl methyl carbinol, was prepared by the method of

Emmerling and Engler (4). This procedure consists of the
reduction of acetophenone by means of metallic sodium. The
yield is comparatively small on account of the pinacone forma-
tion; nor is the purified product very stable for it is slowly con-
verted into the pinacone and acetophenone on standing.
The pure substance is a volatile oil with an odor which simu-
lates that of acetophenone. It boils at 202 to 204#{176}C., under
760 mm. pressure. The specific gravity is 1.013. Polariscopic
examination showed the substance to be in the racemic form.
We found it soluble to the extent of 1.5 per cent in water at
20#{176}C. The aqueous solution may be readily sterilized (in auto-
clave) without diminishing its pharmacological activity.
In all of the following experiments fresh solutions were pre-
pared daily.

TOXICITY OF PHENYL METHYL CARBINOL

The toxicity was studied in white mice by subcutaneous, and

in dogs by intravenous injections of aqueous solutions. The
minimal fatal dose was determined, which amounted to 20 mgm.
for 20 to 25 gram mice. As compared with rose oil it was,
therefore, twice as toxic, and with benzyl alcohol, as reported
by Macht, it was two and a half times as toxic. The presence
of the asymmetric carbon atom thus considerably increased the
toxicity of the alcohol.
In these mice a general anesthesia was induced which lasted
in the non-lethal cases from two to five hours, the respirations
becoming very shallow. In the lethal cases death occurred dur-
ing the anesthesia, and appeared to be the ultimate outcome of
a progressively inhibited respiration.
Two dogs, 10 and 14 kgm. respectively, were given phenyl
methyl carbinol (0.2 gram per kilo body weight) intravenously,
in 3 per cent emulsion in physiological saline solution. In both
instances the dogs died, one during the injection, and the other
 PROPERTIES OF PHENYL METHYL CARBINOL 131

within twenty-four hours. A third dog (10 kgm.) received,

intravenously 0.1 gram per kilo body weight, of 1 per cent solution
in physiological saline. The dog showed no excitement, and no
general anesthesia as in the case of the dog which lived twenty-
four hours. After a few staggering steps the dog became normal
and recovery was rapid and uneventful.
As in the case of the mice, the phenyl methyl carbinol was here
found more toxic than the rose oil and benzyl alcohol, for whereas
in the latter two substances 0.2 gram per kilo body weight was
tolerated very well, a like amount of the former caused death.

ANESTHETIC EFFECT

a. Anesthesia on the tongue. When a drop of pure phenyl

methyl carbinol is placed on the tongue, a burning, tingling
sensation is first experienced, after which the exposed area be-
comes anesthetized without causing necrosis. It compares
favorably with similar applications of rose oil and benzyl alcohol.
b. Anesthesia on the rabbit’s cornea. The minimal concentra-
tion of an aqueous solution of phenyl methyl carbinol, which
would anesthetize the rabbit’s cornea, was determined.
The eye lashes were cut and then 0.5 cc. of the solution, which
was to be tested, was instilled. The eye was held closed for one
minute and then the cornea was touched with the tip of a probe
and observed for the presence or absence of the corneal reflex.
The time of onset of the anesthesia, as well as the time at which
it began to disappear were recorded. The results are tabulated
in table 1.
The results of these experiments indicate that 0.75 per cent
phenyl methyl carbinol is equivalent in anesthetic power upon
the rabbit’s cornea to 1 per cent rose oil and 1.25 per cent benzyl
alcohol. The former, therefore, is more efficient in that respect
than either of the two latter substances.
c. The anesthetic effect upon the human skin as determined by
the wheal method (5). In these experiments phenyl methyl
carbinol was compared with benzyl alcohol relative to the mini-
mal concentrations in physiological saline solution which would
132 AXEL M. HJORT AND CHARLES E. KAUFMANN

anesthetize the skin to light touch. The method of procedure

was described in the paper by Hjort and Eagan (2). The results
are included in table 2.
This table shows that phenyl methyl carbinol anesthetized
the skin in eleven out of twelve cases in per cent solution,
whereas the benzyl alcohol was efficient only in per cent

TABLE 1

The effect of phenyl methyl carbinol on the rabbit’s cornea

SOLUTION ONSET DURATION RESUI/IS

per cent minutes minutes

2 3 Good
1 5 Good
14 24 Good
0.5
Very light
Nil
1 4 Good

2 4 Good
4 Good
2 4 Good
0.75
1 3 Good
14 2 Good
14 2 Good

2 10 Good
2 5 Good
1.0
2 4 Good
2 6 Light

NOTE: Hjort and Eagan (2) found that 1 per cent of rose oil and 1.25 per cent
benzyl alcohol produced efficient anesthesia on the rabbit’s cornea.

solution. The former was also more certain to produce anesthesia

than was rose oil in the same concentration as shown by Hjort
and Eagan (2). Sollmann (6) found that 312 per cent procaine
was the minimal concentration which anesthetized, by the wheal
method. The phenyl methyl carbinol is, therefore, at least as
efficient on the human skin as any known local anesthetic.
 PROPERTIES OF PHENYL METHYL CARBINOL 133

TABLE 2

The effects of phenyl methyl carbinol and benzyl alcohol upon the human skin when
injected intradermally

*In this table: o., indicates onset of anesthesia; d., duration; -‘ no anesthetic
effect; and u., unsatisfactory.
NOTE: Hjort and Eagan (2) in additional experiments with benzyl alcohol
found its minimal effective concentration to be per cent as above.

DISCUSSION

It is evident that the presence of an asymmetric carbon atom

in the phenyl methyl carbinol contributes to it a physiological
activity which is appreciably greater than that of its isomer,
rose oil. However, its local anesthetic properties are not in-
creased in proportion to its toxicity, thus in that respect, at
134 AXEL M. HJORT AND CHARLES E. KAUFMANN

least, it cannot be considered superior to either benzyl alcohol

or rose oil. Likewise the relative instability of the dl phenyl
methyl carbinol makes it of little practical importance as a
local anesthetic.

SUMMARY

1. The following table serves best to compare the physiological

activity of phenyl methyl carbinol with that of benzyl alcohol
and rose oil:

MINIMAL LETHAL MINIMAL

MINIMAL EFFICIENT
DOSE IN MILLIGRAMS CONCENTRATION
ANESTHETIC
PER 20 TO 30 ANESTHETIZING
CONCENTRATION.
GRAMS HUMAN SKIN
RABBIT’S CORNEA
WRITE MICE TO LIGHT TOUCH

per cent percent

Benzyl alcohol 50* 1.2Sf

Rose oil 40f lOOt (n)t
Phenmethylcarbinol 20 0.75

* Macht (1).
f Hjort and Eagan (2). () 13 wheals out of 21.

2. dl phenyl methyl carbinol is a more potent local anesthetic

on the rabbit’s cornea and in the human skin than either its
isomer rose oil or their homologue benzyl alcohol, but not in
proportion to its greater toxic action.
3. The relative instability of the ct-phenethylol offers further
objection to its practical application.
4. The increased physiological action may be due to the
presence of the asymmetric carbon atom.

REFERENCES

(1) D. I.: Journ. Pharm.

MACUT, & Exp. Therap., 1918, xi, 263.
(2) A. M., AND EAGAN,
HJORT, J. T. : Journ. Pharm. & Exp. Therap., 1919, xiv, 211.
(3) CUSHNY, A. R.: Journ. Pharm. & Exp. Therap., 1919, xiii, 71.
(4) EMMERLINO, A., AND ENGLER, C.: Ber. d. Deutsch. Chem. Gesel. (1871), iv,
147; (1873), vi, 1006.
(5) HOFFMANN, A., AND KOCRMANN, M.: Beit. Kim. Chir., 1914, xci, 489.
(6) SOLLMANN, T.: Journ. Pharm. & Exp. Therap., 1918, xi, 69.