A COMPARATIVE STUDY OF HYDRASTINE, BICUCULLINE AND ADLUMINE

¹ Department of Pharmacology, University of Toronto

1. The convulsant, cardiac depressant, depressor, uterine and intestinal stimulant actions of hydrastine are confirmed and the ready detoxification of the drug is demonstrated.

2. Hydrastine and bicuculline are shown to be qualitatively and quantitatively similar, with the exception that bicuculline is approximately 100 times as powerful a convulsant as hydrastine. The convulsions produced by hydrastine and bicuculline are shown to be largely of spinal origin; the rapid detoxification of bicuculline is demonstrated. The difference in disposition of the various groups about the asymmetric carbon atoms (as evidenced by the difference in optical activity) is the probable explanation for the difference in central nervous system toxicity.

3. Adlumine is much less powerful as regards convulsant action; the convulsions produced are of slightly different type; a clonic tremor of the legs is produced; the depressant action on the frog heart is antagonized by atropine and its augmentor effects on uterine tonus and movements are five to ten times as great as those of hydrastine or bicuculline. The modification in action from the hydrastine-type must be due to the effect of replacing the methylenedioxy group in the 6:7 position on the isoquinoline ring of hydrastine or bicuculline with the dimethoxy grouping.

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