BOTANY AND MEDICINE 453 



rect, after all, centuries ago, in attributing considerable benefits to certain 

 yam roots and Strophanthus fruits in the treatment of adrenal hormone and 

 corpus luteum-deficiency diseases. 



Alkaloids. In the realm of alkaloids that can be separated from plants there 

 are many examples of new drugs prepared by chemical modification of existing 

 molecules. This has been especially true among certain tropane types, for 

 example, the cocaine and atropine alkaloids. Since Einhorn prepared the 

 local anesthetic procaine (Novocaine) from cocaine of coca leaves in 1905, 

 a series of other similar local anesthetics (butacaine, Tutocaine, etc.) have 

 been prepared. Homatropine and other atropine synthetic derivatives have 

 likewise resulted from chemical studies of the tropane alkaloids of plants. 



One of the most interesting results from similar investigations of plant 

 alkaloid molecules has taken place in the last five years in the case of the 

 indole alkaloids of the fungus drug ergot, a parasitic fungus infecting rye and 

 other grass in inflorescences. Ergot contains a wealth of pharmacologically 

 active constituents, and about seven physiologically active alkaloids have 

 been isolated from the crude drug. The effects of ergotamine, ergonovine, and 

 ergotoxine as uterine stimulants and oxytocics have, of course, been well 

 established for quite some time. Re-investigations of two ergot alkaloids 

 during recent years have resulted in additional therapeutic uses, such as the 

 relief of migrainous headaches and the treatment of hypertension. Ergotamine 

 was first proposed for migraine by Maier in 1926, but it has only been since 

 about 1948 that some rationale has been suggested for this. The cause of 

 migraine is still not clearly explained, but the recent theory by Wolf relates 

 the intensity of migraine pain to the degrees of pulsation of brain arteries, 

 mainly branches of the external carotid. Ergotamine is known to decrease 

 the amplitude of arterial pulsation. Hence the favorable effects of this 

 fungus alkaloid in migraine relief might be explained on the basis of this 

 action. 



In about 1943 a group of investigators, led by Arthur Stoll in Basel, 

 Switzerland, were able to hydrogenate chemically the natural alkaloids of 

 ergot, particularly ergotoxine. In the meantime, it had been noted that the 

 ergotoxine alkaloid was, in fact, a complex of about three other alkaloids 

 named ergocornine, ergocristine, and ergocryptine. By chemical reduction of 

 ergotamine and the ergotoxine complex their respective dihydro derivatives 

 have been prepared. The interesting result of this from a physiological point 

 of view is the fact that this chemical modification significantly alters several 

 of the effects ascribed to the natural alkaloids (vasoconstriction, oxytocic 

 activity, etc.), especially that of ergotoxine. Ergotoxine dihydrogenated deriva- 

 tives produce very little vasoconstriction, and they decrease arterial pressure. 

 Heart output is slightly decreased. The interest in these plant derivatives for 

 treatment of hypertension comes largely from the fact that hydrogenated 

 compounds depress the vasomotor center in the medulla and possibly stimulate 



