STUDIES ON THE PHARMACOLOGY OF BETA-DIETHYLAMINOETHYLDIPHENYLTHIOACETATE, A SYNTHETIC ANTISPASMODIC

¹ Department of Pharmacology, Medical College of Virginia, Richmond

1. The pharmacological effects of Beta-diethylaminoethyldiphenylthioacetate hydrochloride (23B) as an antispasmodic drug were investigated.

2. The toxicity of the compound as expressed in terms of LD5O was relatively low. The LD5O by intravenous administration was 30 mgm./kg. for the dog, 19.1 mgm./kg. for the rabbit, and 30.5 mgm./kg. for the mouse. The LD5O by intraperitoneal administration was 1500 mgm./kg. for the rat, and 187 mgm./kg. for the mouse. The LD5O by oral administration was approximately 1500 mgm./kg. for the dog, 2720 mgm./kg. for the rat and 700 mgm./kg. for the mouse.

3. Intravenous injection of the compound produced a transient drop in blood pressure proportional to the dose.

4. In the excised rat uterus, addition of the compound 23B to the muscle bath reduced the muscle tone and amplitude of contractions. A concentration 1:78700 or less reduced normal contractions to one-half their former amplitude. A concentration of 1:80800 reduced muscle spasm produced by barium chloride 1:2000 to one half its tonus level in 15 minutes.

5. In the intact rat, subcutaneous administration of 50-100 mgm./kg. of the drug reduced or inhibited uterine contraction. A dose of 75 to 100 mgm./kg. reduced or inhibited spasm produced by administration of Pitocin.

6. In the anesthetized dog the effect of the drug upon intestinal motility was tested. Intravenous doses of 0.5 to 5 mgm./kg. resulted in partial or complete inhibition of intestinal movement, both that normally present and that stimulated by physostigmine. The drug had more effect upon intestinal muscle than upon uterine muscle in the same animal.

7. Normal intestinal contraction in the Thiry-Vella loop of the unanesthetized dog could be inhibited by intravenous administration of 5 mgm./kg. of 23B. The same dose reduced the stimulated contraction induced by physostigmine.

8. The compound 23B was effective in checking diarrhea in mice. The incidence of diarrhea produced by 500 mgm./kg. of senna was reduced to 61 per cent of the incidence among control animals by administration of 50 mgm./kg. of 23B.

9. The decrease in salivary flow produced by 0.5 mgm./kg. of the drug corresponded to that produced by 0.0025 to 0.005 mgm./kg. atropine sulfate.

10. Local irritation of the rabbit skin and of the rabbit eye was produced by solutions of the drug of 0.5 per cent strength or greater.

11. The local anesthetic effect of 1.0 per cent cocaine hydrochloride was duplicated by 0.125 per cent 23B.

12. The drug had no effect upon the size of the pupil of the rabbit eye.