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Journal of Pharmacology And Experimental Therapeutics, Vol. 94, Issue 3, 249-261, 1948
Copyright © 1948 by American Society for Pharmacology and Experimental Therapeutics

A NEUROLOGICAL SYNDROME INDUCED BY ADMINISTRATION OF SOME CHLORINATED TERTIARY AMINES

A. GOLDIN 1, H. A. NOE 1, B. H. LANDING 1, D. M. SHAPIRO 1, and B. GOLDBERG 1

1 Biology and Pathology Sections, Medical Division, Army Chemical Center, Maryland; Department of Preventive Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland

1. A series of nitrogen mustard analogues were studied and the essential structural groupings necessary to produce the neurological syndrome of waltzing in mice were identified.

2. The compounds which produced the waltzing syndrome were dialkyl and heterocyclic-beta-chloroethylamines.

3. No waltzing was elicited when the following structural modifications were made:

a) Substitution of a hydroxyl group for the beta chlorine.

b) Substitution of a beta-phenyl group for one of the beta hydrogens in the chlorinated chain.

c) Substitution of bromine for the beta chlorine.

d) Introduction of phenyl groups into the dialkyl carbons.

4. Primary and secondary beta-chloroethylamines; related quaternary compounds; and bis, tris, and tetrakis beta-chioroethylamines did not elicit the effect.

5. Two compounds similar in structure to both the mono-beta-chloroethyl amines and bis(beta-chloroethyl)amines produced transient waltzing.

6. Cerebellar and axial lesions found in induced waltzers could account for the behavior pattern of the mice.

7. The chemical relationships of these compounds and their mechanism of action are discussed.

Submitted on July 23, 1948




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Copyright © 1948 by the American Society for Pharmacology and Experimental Therapeutics.