A COMPARATIVE STUDY OF THE PHARMACOLOGY OF CERTAIN CRYPTOPINE ALKALOIDS

¹ Laboratories of Gordon A. Alles, Ph.D., Pasadena, California

1. The cardiac inhibitory effects of cryptopine and protopine are similar to that of allocryptopine (-fagarine) on the isolated auricle. Berberine, a compound quite closely related in structure to the cryptopine alkaloids, is far less active in this respect. Amarin, papaverine and quinidine were comparatively valued.

2. Intravenous doses of 4 x 10^-6 to 2 x 10^-5 moles per kgm. of the cryptopine alkaloids cause moderate pressor effects, and larger doses cause depressor effects. The alkaloids were not notably different in causing these effects. In addition, all of these alkaloids in these doses were found to cause occasional cardiac arrhythmias and sensitization to epinephrine induction of cardiac arrhythmias. These latter effects were similar to the effects of amarin.

3. On the isolated heart the cryptopine alkaloids were active coronary dilators comparable to papaverine, protopine being somewhat the most active and as active as papaverine. Amarin was similarly active, and all compounds caused some reduction in cardiac amplitude or rate, or both, in the range of dosage required for coronary dilator activity.

4. On isolated ileum biphasic responses were noted, but. with concentrations in the range of 10^-4 to 5 x 10^-4 molal, contraction was the usual response and protopine appeared to be somewhat the most active. With repeated addition of compounds to the ileum relaxing or blocking effects became evident.

5. Acute lethal toxicity was not greatly different for the cryptopine alkaloids, but protopine was somewhat the least toxic. Berberine was distinctly more toxic and produced marked depression in contrast to the stimulation noted following the cryptopine alkaloids.