Chinese Journal of Physiology

COMPARATIVE TOXICITY OF EPHEDRINES 91

Three to five minutes after administering ephedrine the animal becomes restless and is easily excited. Defecation, urination and efforts to vomit follow almost immediately and in ten to fifteen minutes the whole body trembles, especially the head. There is erection of the tail and hair and very soon there follows a series of violent convulsions. The animals often scream and leap high in the air. They are very sensitive to mechanical stimuli. The excitement and convulsions continue a long time. Atter thirty to sixty minutes the convulsions gradually decrease, the animal collapses on its abdomen and respiration becomes irregular and slow. Death occurs in I to 24 hours.

While pseudoephedrine produces similar symptoms the period oi excitement is short, the animal soon lies on its abdomen and shows extreme difficulty in breathing. Death occurs in 20 to 60 minutes.

DISCUSSION

Our results in general show that in frogs, rats, rabbits and dogs ephedrine is definitely more toxic than ephetonin and pseudoephedrine. Our M.L.D. of ephedrine in the white rabbit intravenously confirms the result of Kreitmair. We do not agree with Chen’s results (38) which show an identical toxicity for ephedrine and ephetonin.

in comparing ephedrine with pseudoephedrine our results are similar to those obtained by Fujii (6), though the ratio is nearer 1.4 than 1.6, as found by a little more careful measurement. From our knowledge of these drugs and the symptoms observed we conclude that in most animals death is due primarily to collapse of the heart due to depression of the muscle. Inthe hamster there isso much respiratory embarrasment that failure of respiration would appear to play a more important role as a cause of death. We suggest this as a possible explanation for the results from mice, in which one sees a similar inversion of the proportionate toxicity of ephedrine and ephetonin.

Seeing that ephetonin is not so strong or toxic a drug as ephedrine, we recommend that due consideration be given to adjustment of its therapeutic dose, and in comparing the minor toxic effects of these two isomers a proportionate dosage be taken as a basis of judgment regarding their untoward effects.

SUMMARY

1. The comparative toxicity of ephedrine, ephetonin and pseudoephedrine, as tested in frogs, rats subcutaneously, gray rabbits intravenously and subcutaneously, white rabbits and dogs intravenously, is in