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Journal of Pharmacology And Experimental Therapeutics, Vol. 110, Issue 4, 463-469, 1954
Copyright © 1954 by American Society for Pharmacology and Experimental Therapeutics

ORAL AND INTRAVENOUS ADRENOLYTIC ACTIVITY OF A NUMBER OF N-BENZYL-N-PHENOXYETHYL AND N-BENZYL-N-PHENOXYISOPROPYL-beta-CHLORETHYLAMINES

E. J. Fellows 1, R. A. McLean 1, E. Macko 1, J. F. Kerwin 1, O. C. Hall 1, F. J. Milnes 1, I. H. Witt 1, and G. E. Ullyot 1

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

Various modifications of N-benzyl-N-phenoxyethyl- and N-benzyl-N-phenoxyisopropyl-beta-chlorethylamine have been investigated for oral and intravenous adrenergic blocking activity.

Appraisal of the relationship between structure and activity in these series of compounds disclosed a lack of direct correlation between intravenous and oral potency.

One compound, N-benzyl-N-phenoxyisopropyl-beta-chlorethylamine HCl, 688-A, was found to have a high degree of intravenous adrenergic blocking activity. Its oral effectiveness is outstanding among the beta-chlorethylamines.

The principal pharmacologic action of 688-A appears to be blockade of the vasoconstrictor action of epinephrine of l-arterenol.

Toxicity studies indicate that 688-A possesses a wide margin of safety.

The ratio between emetic dose and effective dose suggests that adrenergic blockade may be attained clinically without the complicating side effects of nausea and vomiting.

Submitted on December 26, 1953






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Copyright © 1954 by the American Society for Pharmacology and Experimental Therapeutics.