Experimental Pharmacological Study of Mono-Brom-Hydroxy-Benzyl Alcohol

Abstract

Macht, Dunning and Stickels 1 described the preparation and some of the pharmacological properties of a large number of derivatives of hydroxy-benzyl alcohol, commonly known as saligenin. Further investigation of the compounds pointed to the mono-brom-hydroxy-benzyl alcohol as being the most interesting of the series, and a more intensive and extensive study of that compound was accordingly begun.

Mono-brom-hydroxy-benzyl alcohol, named bromsalizol for convenience, is a white crystalline compound, melting at 107.5°–109°C., which on tasting, produces a numbness of the mucous membranes of the mouth and tongue. Its formula is with the bromine in the para-position. The analogous compounds with halogen atoms in the ortho- and meta-positions in the benzene ring have also been prepared in our laboratories. Bromsalizol is soluble in water to the extent of 0.5% and is freely soluble in alcohol and olive oil.

When studied on lower and higher animals, the toxicity of bromsalizol was found to be quite low. The minimal lethal dosage for some of the higher animals is shown in Table I. Doses of from 5 to 10 grains (0.3 to 0.6 gm.) have been repeatedly ingested by a large number of men without any discomfort or untoward effect.

The two salient pharmacodynamic properties exhibited by bromsalizol, even when employed in small doses or low dilutions, are (1) its antispasmodic or relaxant effect on smooth muscle tissues and organs, and (2) its local anesthetic effect. Its action on smooth muscle was studied in situ on intestines of cats, rabbits and rats, and much more extensively on all kinds of smooth muscle preparations from excised organs of the cat, rabbit, guinea pig, rat, bear, woodchuck and other animals. Experiments on excised muscle strips from the intestines, uterus, gall bladder, urinary bladder, fallopian tubes, ureters and other organs showed that the drug in dilutions of from 1 :10,000 to 1 :50,000 lowered the tonus of smooth muscle and slowed or completely inhibited the rhythmic contractions without killing the tissue, however, as could be proven by subsequent application of a suitable pharmacological stimulus. (Fig. 1.)