STUDIES ON VERATRUM ALKALOIDS. XXXVII. CHRONOTROPIC CARDIAC ACTION AND TOXICITY OF N-ALKYL DERIVATIVES OF VERATRAMINE

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

Some pharmacological properties of N-methyl, N-ethyl, N-n-propyl, N-n-butyl, N-n-pentyl, N-n-hexyl, N-isobutyl, N-benzyl, N-methyl methiodide and N-n-butyl methiodide derivatives of veratramine have been examined.

In the regular homologous series extending from N-methyl to N-n-hexyl compounds, an orderly spectrum of antiaccelerator activity in dog heart-lung preparations was found. Activity was low with N-methylveratramine, progressively increased to a peak with the N-n-butyl homolog, which had two-thirds of the activity of veratramine itself, and then decreased with further lengthening of the chain. The N-isobutyl derivative possessed only a tenth of the activity of its straight chain isomer and the N-benzyl compound was also relatively inactive.

The antiaccelerator activity of the compounds was closely paralleled by their negative chronotropic potencies in the dog heart-lung preparation and in the isolated atrium of the guinea pig, by their ability to produce periodic cardiac rhythms, and their intravenous toxicity in mice.

The quaternary methiodide derivatives were virtually devoid of antiaccelerator activity and produced a different pattern of toxic effects when injected intravenously in mice.