BLOCKADE OF THE NICOTINE ACTION ON THE BLOOD PRESSURE BY THIAZOLE-COMPOUNDS (SULFATHIAZOLE AND THIAMINE)

¹ From the Merck Institute for Therapeutic Research, Rahway, N. J., and the Pharmacological Laboratory of the Mount Sinai Hospital, New York, N. Y.

1. The intravenous infusion of sodium sulfathiazole (about 60-150 mgm. per kgm. body weight) or of thiamine hydrochloride (about 3-10 mgm. per kgm. body weight), prevents the rise in blood pressure induced by the intravenous injection of 0.1-1.0 mgm. nicotine base in untreated cats.

2. This blocking of the nicotine effect is not caused by a paralysis of the synapses; it lasts 10 minutes to 1 hour or more and is dependent directly in its duration and intensity upon the amount of sulfathiazole or thiamine infused and inversely upon the test dose of nicotine used.

3. The blocking of the nicotine action upon autonomous ganglia is produced essentially by the thiazole group of the sulfathiazole and thiamine; thiazolefree sulfonamides, such as sulfanilamide, sulfadiazine and sulfapyrazine, did not show this effect even in large dosages.

4. The interference with the nicotine effect is probably caused by a transient binding of the thiazole-containing drugs at or inside the sympathetic ganglia as well as at the cells of the adrenal medulla, thus producing a selective displacement of nicotine and its action. It would seem that enzymatic processes in or at these nerve cells are involved.

5. The blockade of the nicotine action which inhibits the rise in blood pressure caused by nicotine, does not seem to influence the vagal and sympathetic ganglia of the heart.

6. The nicotine-like blood pressure effect of acetylcholine induced by stimulation of the sympathetic synapses and the adrenal medulla in the atropinized animal, remains unchanged in the presence of a thiazole induced blockade of these same ganglia to nicotine; the effect upon the blood pressure of adrenaline, carbaminoyl choline and acetyl--methylcholine likewise remain unchanged.

7. The sodium salt of para-amniobenzoic acid proved incapable of producing or abolishing a blockade of sympathetic ganglia.