CONTRIBUTION TO THE PHARMACOLOGY OF THE BENZOTHIAZOLES

¹ From the Laboratory of Organic Chemistry of Columbia University, and the Laboratories of the New York Homeopathic Medical College and Flower Hospital

1. The following pharmacological effects were observed with both benzothiazole and its 2-amino derivative:

a. Small doses were followed by initial stimulation of the respiratory center, and larger ones by depression and paralysis of the same, resulting in collapse of the animal, stupor, or occasional convulsions, rapid and shallow breathing, and increased reflex excitability.

b. Except in toxic doses, they had but little action upon the heart muscle or the pulse. Large doses, however, always caused lowering of the blood pressure, with ultimate paralysis of the vasomotor center. The heart failed through asphyxia and not because of any direct action upon it.

2. Benzothiazole itself caused a dermatitis resembling that produced by poison ivy. Blondes were more susceptible to its action than brunettes. Sex was without influence upon this sensitivity. The reaction may be delayed for days and sensitization may be increased by repeated application. Man was more susceptible to the action of this compound than the other organisms tested. In the rat, it produced anuria.

3. The effects of 2-aminobenzothiazole, in addition to those mentioned under (1), and more specifically, were as follows:

a. Respiration: Doses of more than 1 cc. of n/22 HC1 per kilogram of animal caused greater depth of breathing but no variation in the rate. When the thiazole was dissolved in the same concentration of acid and administered in the same volume doses, the depth of breathing was diminished and the rate accelerated the total ventilation remaining practically unchanged. Overdoses killed by respiratory paralysis.

In all of the experiments with non-acid saline as solvent, the effect upon the cat or rabbit was similar in general to that of the acidic solution but, owing to the low minute concentrations, the results were less decisive.

b. Circulation and heart muscle : The blood pressure was lowered, and ultimately the vasomotor center was paralyzed. The heart muscle and pulse rate were affected but little, excepting after overdoses.

C. Striated muscle : In the frog, the gastrocnemius muscle promptly and completely lost its irritability.

d. Conjunctiva: In the rabbit, there was neither local nor central action when the thiazole was applied to the sac.

e. Uric acid: The uric acid in the blood of the cat and rabbit was apparently increased.

f. The maximum tolerated dose was approximately 0.016 gram per kilogram of body weight in the case of the cat.

4. Preliminary pharmacological tests were carried out also with dehydrothio-p-toluidine, 2-anilino-benzothiazole, 2-phenyl-benzothiazole and the 5-carboxylic acid of the latter.