STUDIES ON DERIVATIVES OF 2,2-BIS-(p-CHLOROPHENYL)-1, 1-DICHLOROETHANE (DDD, TDE) WITH SPECIAL REFERENCE TO THEIR EFFECTS ON THE ADRENAL CORTEX

¹ Department of Pharmacology, Medical College of Virginia, Richmond

Studies on derivatives of 2,2-bis-(p-chlorophenyl)-1,1-dichloroethane (DDD) have contributed the following information concerning the action of this class of compounds on the adrenal cortex.

In dogs, the biochemorphologic studies of Larson et al. (1955) have been extended. Substitutions in the p-phenyl positions may markedly affect the property of producing adrenal cortical atrophy. Thus the methoxy and nitro derivatives were found to be inactive whereas the methyl derivative produced severe atrophy. Substitution of an aldehyde group for the dichloroethane moiety of the molecule gave negative results.

Refractoriness of the adrenal cortex of the rat to production of atrophy by this class of compounds was repeatedly demonstrated. Thus, after oral administration of the methyl derivative as well as of 2,2-bis-(p-chlorophenyl)-1,1-dibromoethane and 2,2-bis-(p-ethylphenyl)-1,1-dibromoethane there was no histological evidence of atrophy. Further, superimposition of orally administered 2,2-bis-(p-ethylphenyl)-1,1-dichloroethane (Perthane), which is active in the dog (Finnegan et al., 1955), on the gland undergoing atrophy from cortisone treatment or hypertrophy from ACTH injection did not intensify the atrophy produced by cortisone or induce atrophy in the ACTH-stimulated gland. Lastly, parenteral administration of DDD and of Perthane did not result in adrenal cortical atrophy, contrary to the claim of Verne and Wegmann (1952) for DDD.

In the study in which Perthane was given simultaneously with ACTH, hypertrophy occurred but to a significantly lesser degree as compared to control ACTH- treated rats. A similar result was not obtained when the experiment was repeated on hypophysectomized rats.

Pursuant to the possibility that functional effects may be exerted on the adrenal cortex of the rat by DDD or derivatives of it, Perthane was administered to alloxan-induced and partially depancreatized diabetic animals for prolonged periods. As judged by blood sugar levels, no amelioration of the diabetic state was produced. This is contradictory to reports of studies with DDD (Brown 1953b).

Finally, since differences in metabolic pathways could account for the apparent species specific atrophying effect on the adrenal cortex of the dog, preliminary observations are reported bearing on the metabolism of C¹⁴-labeled Perthane in the rat. Excretion of the C¹⁴ label is predominantly via the bile and feces in the rat whether the material is administered orally or intravenously.