THE PHARMACOLOGICAL AND TOXIC ACTIONS OF DEXTRO- AND LAEVO-MIOTINE

¹ Welcome Physiological Research Laboratories, Langley Court, Beckenham
² Department of Medical Chemistry, University of Edinburgh

1. Dextro- and laevo-miotine have the same action as physostigmine.

2. The laevo-isomeride is more toxic than the dextro-isomeride in all the species tested, namely, mouse, guinea pig, rabbit, hen and duck. Both isomerides potentiate the toxicity of acetyl choline.

3. The action of l-miotine on the cat blood pressure is greater than, but similar to that of d-miotine. The normal acetyl choline effect on blood pressure is potentiated by a previous dose of either isomeride. Large preliminary doses may lessen the acetyl choline response considerably. The nicotine action of acetyl choline is also potentiated. Similar effects are obtained with other choline esters such as propionyl choline.

4. The laevo-isomeride is more active on the frog heart and also on the salivary secretion in the cat.

5. In most species examined the laevo-isomeride was the more powerful miotic. The ratios of the relative activities of the two isomerides however, varied.

6. Laevo-miotine is approximately eight times more powerful an antagonist of curare than is dextro-miotine when tested on the cat's sciatic nerve preparation. L-miotine also antagonizes strychnine methiodide.

7. Laevo-miotine is about four times more active on the isolated rabbit intestine than dextro-miotine. A similar ratio holds for the rabbit's vas deferens in vitro. Similarly the l-isomeride is four times more active in potentiating the acetyl choline response of the intestine than the d-isomeride.

8. On the guinea-pig uterus the direct action of the laevoisomeride is greater than that of the dextro-isomeride, and it has a more powerful potentiating effect on the acetyl choline response.

9. Laevo-miotine is four times more active in potentiating the acetyl choline response of leech muscle than dextro-miotine.

10. The relative inhibitory activities of d- and l-miotine on serum choline esterase vary in different species, the dextroisomeride being more active in the fowl and man. In all other species examined, the laevo-isomeride was the more active.

There is no constant direct relationship between toxicity and the inhibition of serum choline esterase, as tested by our method.