THE SPASMOLYTIC AND LOCAL ANESTHETIC ACTION OF SOME DERIVATIVES OF FLUORENE-CARBOXYLIC ACID AND RELATED COMPOUNDS

¹ From the Department of Pharmacology, University of Louisville School of Medicine Louisville, Kentucky

1. Forty-one compounds, esters of diphenylacetic and diphenyleneacetic acids, and related compounds, have been studied for spasmolytic and local anesthetic actions, and toxicity, in comparison with atropine, "Syntropan," "Trasentin," and papaverine.

2. Relaxation of spasm of the small intestine in vitro produced by acetylcholine ("neurotropic action") and relaxation of the spasm produced by histamine and barium ("musculotropic action") have been determined. The relaxing action on the small intestine in vivo in rabbits, guinea pigs, and dogs, has been observed. Changes in structure give a wider variation in neurotropic potency than in musculotropic potency.

3. Local anesthetic action is related more closely to musculotropic action than to other properties.

4. The introduction of a carbon-carbon linkage in esters of diphenylacetic acid, giving diphenyleneacetic acid (fluorene-carboxylic acid) derivatives, results, in most cases, in an increase in spasmolytic potency with little or no increase in toxicity.

5. The most promising compound, diethylaminoethyl-fluorene-9-carboxylate, has a spasmolytic potency varying from one-seventh to 20 times that of atropine, depending upon the test object. In antagonizing the vascular action of acetylcholine, atropine is 130 times stronger, in mydriatic action atropine is 5000 times stronger, and in antisialogogue action atropine is more than 100 times stronger than this compound.

6. Diethylaminoethyl fluorene-9-carboxylate warrants clinical trial as a spasmolytic agent.