PHARMACOLOGY STUDIES ON BIS-(1-CARBO--DIETHYL-AMINOETHOXY)-1-PHENYLCYCLOPENTANE)-ETHANE DISULFONATE

¹ Research and Development Division, Smith, Kline & French Laboratories, Philadelphia, Pa.

1. 6-Dimethylamino-4,4-diphenyl-3-heptanone hydrochloride, codeine and bis-(1-(carbo--diethylaminoethoxy)-1-phenyl-cyclopentane)-ethane disulfonate (SKF No. 769-J₂) were found to exhibit antitussive activity when tested by a modification of the Domenjoz method. 3,3-Diethyl-2,4-dioxopiperidine was ineffective in doses up to 100 mgm./kgm.

2. In effective antitussive doses, SKF No. 769-J₂ produced either an increase or slight decrease in respiratory volume in dogs, whereas codeine caused a marked decrease.

3. SKF No. 769-J₂ had 1/2 to 1/10 the antispasmodic activity of atropine on the isolated rabbit intestine, and 1/2 the local anesthetic activity of cocaine on the rabbit cornea.

4. In subacute and chronic toxicity studies, no evidence of changes due to administration of SKF No. 769-J₂ was observed by histological examination of tissues removed from rats and dogs which received massive daily doses of this compound for periods of 1 to 3 months.

5. The data obtained in the present experiments indicate that SKF No. 769-J₂ should be evaluated clinically as an antitussive agent.